The study authors found that this was especially true in discussions concerning antiretroviral adherence.

“Half the time people don’t take their meds as prescribed, whether it’s antiretrovirals or antihypertensives [high blood pressure medication] or diabetes meds,” said M. Barton Laws, an assistant professor of health services policy and practice at Brown University and lead author of the study, in correspondence with The AIDS Beacon. “The problem is that physicians often don’t even know this, and if they do, they misdiagnose the reasons and respond ineffectively. Just repeating the information that if you don’t take the meds, you’ll get sick and maybe die is not helpful because, obviously, people have already been told this innumerable times, so the problem is not that they don’t know it.”

“People don’t want to be scolded, so they don’t tell the doc they have been non-adherent and try to avoid these discussions or just say ‘Okay then’ to get them over with,” he added.

Laws noted that physicians may need more training in learning how to help patients with problems such as treatment adherence.

“Just telling people what to do misses the point, and getting frustrated with them when they don’t do what you want usually just makes matters worse. But creating effective partnership is a skill,” said Laws. “Doctors can’t be expected to just automatically be good at it, but it isn’t taught in medical school and what doctors learn from their residencies depends on who their role models happen to be, there really isn’t anyone in charge.”

“I think that physicians gaining better skills at shared decision making and eliciting patient engagement is essential to the whole movement toward patient centeredness in the organization, financing, and delivery of health care. It’s that interaction between two people where it all ultimately happens,” said Laws.

Poor adherence to highly active antiretroviral therapy can lead to higher viral loads (amount of HIV in the blood), decreased CD4 (white blood cell) counts, and increased resistance to antiretroviral medications.

Studies have shown that approximately 50 percent to 80 percent of people living with HIV have difficulty adhering to their antiretroviral regimens. Typically, clinicians recommend taking at least 95 percent of prescribed doses to avoid treatment failure.

According to the study authors, research has shown that good patient-provider communication is linked to better medication adherence and treatment outcomes.

In this study, researchers recorded visits between 45 HIV care providers and 415 HIV patients from four HIV specialty clinics in the United States. The goal of the study was to see how often clinicians spoke with their patients about treatment adherence and determine what the quality of those discussions was.

The conversations were analyzed using a system that defined and counted how often various verbal behaviors occurred for physicians and patients. For instance, the researchers monitored the number of questions versus orders between physicians and patients.

Monitored topics included specific strategies to achieve antiretroviral drug adherence; issues such as substance abuse, recovery, emotions, personal relationships, and social services; medical issues, such as appointments and prescriptions; and casual conversation.

All HIV patients were 19 years or older, spoke English, and had at least one prior visit with their provider. Most participants (78 percent) reported taking antiretrovirals at the time of the study.

Two-thirds (66 percent) of the patients were men, and 59 percent were African-American. Almost half of all patients reported being disabled, and 54 percent reported having diabetes, high blood pressure, and/or hepatitis.

In addition, 27 percent of participants reported current illegal drug use and 49 percent reported a history of alcohol abuse, although most did not use alcohol at the time of the study.

Women in the study were less likely than men to have at least a high school education (59 percent versus 79 percent).

Results showed that some discussion of adherence occurred with almost 89 percent of patients who said they were on antiretroviral drugs. However, discussion of antiretroviral adherence was minimal, accounting for less than 6 percent of the total visit time in cases where it occurred. Adherence problem solving occurred in only 15 percent of visits with patients on antiretrovirals and with only 23 percent of those with adherence problems.

Apart from the physical exam at each visit, providers made almost 56 percent of all remarks and asked five times as many questions as patients. The ratio of provider to patient requests, instructions, and recommendations per visit was 22 to 1.

On average, requests, instructions, and recommendations formed 20 percent of clinician remarks during adherence problem-solving discussions, compared with 8 percent while discussing biomedical issues and none while discussing psychosocial aspects with patients.

The researchers found that clinicians asked few open questions or questions that elicited patient opinions or preferences. They also found that physicians rarely checked patients’ understanding, especially in adherence problem-solving.

For more information, please see the study in AIDS and Behavior (abstract) or the press release from Brown University.

The study authors noted that the rate of low muscle mass was similar to that found for HIV-negative men aged 70 to 74 years old in a different study.

The investigators suggested that evaluation for muscle loss should be included when assessing bone fracture risk in people with HIV. They stressed the need for future studies that examine the impact of decreased muscle mass and function on physical wellness and quality of life for people with HIV.

Previous studies have suggested that premature aging, including changes in the muscle, bone, and nervous systems, are common in people with HIV. Some researchers believe HIV itself causes premature aging in people with the disease; there are also indications that some antiretrovirals, including older drugs such as zidovudine (Retrovir) and stavudine (Zerit), may be responsible for premature aging (see related AIDS Beacon news).

Sarcopenia is the loss of muscle mass, strength, and function associated with aging. According to the study authors, multiple factors, including poor nutrition, inflammation, and hormonal changes, are thought to contribute to age-related muscle loss. Disability, hospitalizations, increased risk of falls, lower quality of life, and increased risk of death are some possible outcomes of the disease.

The study authors noted that screening for sarcopenia is relatively easy and can be done with muscle function tests, including gait speed and balance tests.

In this study, investigators examined the rate of age-related muscle loss and potential risk factors for the condition, including low muscle mass, low bone mineral density, and lipodystrophy (abnormal body fat redistribution), in HIV-positive men.

The study included 66 men with HIV with a median age of 42 years old. About 14 percent of the men were previously untreated; the rest were treatment-experienced. On average, the previously treated men were about 10 years older, had HIV longer, and had lower CD4 nadir counts (the lowest CD4, or white blood cell, count measured after infection) than treatment-naïve men.

Results showed that 19 percent to 22 percent of the men had low muscle mass, and 68 percent had low bone mineral density. In addition, between 42 percent and 55 percent of the men had lipodystrophy.

There was no difference in the frequency of low muscle mass or low bone mineral density in previously treated versus treatment-naïve men. Low muscle mass and low bone mineral density were both associated with a lower body mass index.

Men with low bone density were also more likely to have been treated with non-nucleoside reverse transcriptase inhibitors and drugs such as zidovudine or stavudine.

Lipodystrophy was highly associated with antiretroviral therapy, including treatment with protease inhibitors and nucleoside reverse transcriptase inhibitors. However, lipodystrophy was less common in men with low muscle mass.

For more information, please see the study in the Journal of Clinical Densitometry (abstract).

The study also showed that teens with HIV acquired from their mothers during pregnancy or childbirth were significantly less likely to get Pap smear tests than teens with behaviorally-acquired HIV.

The study investigators suggested that prevention of human papillomavirus, a primary cause of cervical cancer, through vaccination may be especially beneficial among HIV-positive, female teens who acquired HIV from their mothers. They also stated that clearer guidelines on initiation and frequency of Pap screening in this population of HIV-positive women may be necessary.

HIV in women is associated with an increased risk of acquiring human papillomavirus (HPV), one of the most common sexually transmitted infections. Previous research has shown that around 75 percent to 80 percent of HIV-positive women also have HPV.

In addition, women with both HIV and HPV are at an increased risk of cervical cancer (see related AIDS Beacon news), which is primarily caused by HPV. Researchers estimate that 20 percent to 60 percent of HIV-positive women show signs of pre-cervical cancer.

Pap tests, also called pap smears, detect the presence of abnormal or cancerous cells in the cervix. According to the study authors, these tests have been shown to reduce cervical cancer rates by 60 percent to 90 percent.

Although the American Cancer Society recommends regular Pap tests for women with HIV, it does not address the timing of initial Pap screening for teens with HIV acquired from their HIV-positive mothers at birth (called perinatally-acquired HIV). Guidelines for HIV-negative women recommend screening within three years of becoming sexually active or at age 21.

According to the study authors, most patients with perinatally-acquired HIV are seldom perceived as a high-risk group for HPV infection because most of them have been cared for since infancy in pediatric clinics. However, recent studies have shown that sexual activity, sexually transmitted infections, and pregnancy in this population are common.

In this study, the researchers compared cervical cancer screening rates in teens with perinatally- versus behaviorally-acquired HIV. They also monitored rates of abnormal Pap test results in both groups.

The study included 231 sexually active HIV-positive women aged between 13 and 24 years old from 20 clinical sites across the United States. About 46 percent had perinatally-acquired HIV. Thirteen percent had a record of HPV infection, over 36 percent had a current or past sexually transmitted infection, and 52 percent were pregnant at least once between 2001 and 2006.

Results showed that 58 percent of Pap test results were abnormal. However, most of the abnormalities identified in the study were low-grade lesions. Only 2 percent of patients had high-grade lesions.

Having a sexually transmitted infection was associated with an increased likelihood of abnormal Pap test results, although the authors noted that this may be because women with sexually transmitted infections are viewed as a high-risk group by clinicians, who are thus more likely to recommend cervical cancer screening.

In addition, patients with CD4 (white blood cell) counts less than 200 cells per microliter were twice as likely to have an abnormal Pap test result.

Results also showed that less than half the participants had one or more Pap test between 2001 and 2006.  Women with perinatally-acquired HIV were 34 percent less likely to have undergone Pap tests than women with behaviorally-acquired HIV. African-American women were 26 percent less likely to have undergone Pap tests compared with Caucasians. The researchers suggested that the latter may be due to socioeconomic differences.

Patients 21 years or older and patients with a history of any sexually transmitted infection or pregnancy were more likely to get a Pap smear test. Participants managed at clinics with an on-site adolescent medicine specialist were 20 percent more likely to have a Pap test and 31 percent less likely to have an abnormal Pap test result as teens managed at pediatric clinics.

Nineteen percent of abnormal Pap test results had reverted to normal by the end of the study.

For more information, please see the study in the Journal of Pediatric and Adolescent Gynecology (abstract).

In particular, by week 72 of the study, three to five times as many patients who deferred treatment had progressed and required antiretroviral therapy than patients who had begun treatment soon after infection. Patients who were treated early initially and then stopped treatment also went significantly longer before additional therapy was necessary.

“The higher than anticipated rate of disease progression among untreated individuals…is a compelling finding of this study and contributes to the growing body of evidence favoring earlier treatment,” wrote the study authors.

“Our results suggest that if immediate therapy is not begun, progression to meeting standard criteria for antiretroviral therapy initiation may occur more rapidly than expected, especially with changing treatment paradigms,” they wrote.

As a result of the large difference between outcomes, the study’s safety monitoring board recommended that it be stopped early.

Previous research has shown that starting antiretroviral treatment early after infection with HIV improves later viral loads, but study findings have been mixed.

According to the study authors, attempts to assess the effect of antiretroviral therapy on viral set point (the point at which the amount of HIV in the blood naturally levels off) in newly infected people have been limited to date, largely because of the difficulty of identifying recently infected individuals.

In this 96-week trial based in the United States and Peru, researchers set out to test whether starting treatment soon after infection would affect the viral set point later, as well as other outcomes such as disease progression.

The study included 130 men and women who were infected with HIV within the last six months but were beyond the acute phase of infection. Individuals in one group received 36 weeks of antiretroviral therapy immediately, then discontinued treatment; a second group deferred treatment until it was necessary due to disease progression.

Patients in either group who required treatment initiation or re-initiation, respectively, due to disease progression were advised to start antiretroviral therapy.

Participants were randomly assigned to the immediate treatment or deferred treatment group.  All participants were previously untreated and had HIV viral loads of at least 500 copies per milliliter.

Treatment consisted of Truvada (emtricitabine/tenofovir) plus Kaletra (lopinavir/ritonavir).

Results showed that by the end of the study, 36 percent of participants in the deferred treatment group required antiretroviral treatment initiation due to low CD4 (white blood cell) counts, high viral loads, or AIDS, compared with 11 percent in the immediate treatment group.

In addition, 20 percent of patients in the deferred treatment group required therapy within the first 36 weeks of the study and 8 percent of participants in the deferred treatment group progressed to AIDS.

Further analysis showed that, including only participants who completed the full 72 weeks of the study period, 50 percent in the deferred treatment group and 10 percent in the immediate treatment group required antiretroviral therapy. Twenty-eight percent of participants in the deferred group required treatment in the first 36 weeks of the study.

Outcomes were better for the immediate treatment group than the deferred treatment group at weeks 36 and 72, as determined by factors such as viral load and disease progression. After stopping initial treatment, participants in the immediate treatment group also took significantly longer to progress to the point at which antiretroviral therapy was necessary than people in the deferred treatment group.

On average, individuals who received immediate antiretroviral therapy experienced an extra 16 weeks beyond the 36 weeks of treatment before their disease began to progress.

However, after 72 weeks, the average viral load was similar in both groups.

Participants with initial CD4 counts of less than 540 cells per microliter or viral loads above about 25,000 copies per milliliter were more likely to require antiretroviral therapy earlier.

Due to the early study discontinuation, the authors were not able to determine whether immediate versus deferred treatment had any effect on viral load set point.

For more information, please see the study in The Journal of Infectious Diseases.

“These positive two-year data indicate that elvitegravir has the potential to be an important new once-daily treatment option for people living with HIV who have developed resistance to other therapies,” said Norbert Bischofberger, executive vice president of Research and Development and chief scientific officer of Gilead Sciences, which is developing elvitegravir, in a press release.

“In addition, we are very excited about elvitegravir’s role as part of our new Quad single-tablet regimen, which is currently in U.S. regulatory review,” he added.

Gilead stated that based on the results, the company plans to file for approval of elvitegravir from the United States Food and Drug Administration (FDA) in the second quarter of 2012.

Gilead also submitted a new drug application for its investigational Quad pill (cobicistat/elvitegravir/emtricitabine/tenofovir) to the FDA in October (see related AIDS Beacon news).

Elvitegravir belongs to a relatively new class of antiretroviral called integrase inhibitors. Currently, Isentress (raltegravir) is the only approved integrase inhibitor. It is approved both as a first-line treatment for HIV and for people who are treatment-experienced.

Gilead previously presented 48-week results from the Phase 3 clinical trial showing that elvitegravir was comparable in safety and efficacy to Isentress (see related AIDS Beacon news). On Friday the company released the full 96-week results.

The study included 702 participants, a majority of whom (63 percent) were resistant to two or more classes of antiretrovirals at the start of the trial.

Participants were randomly assigned to receive once-daily elvitegravir (150 mg or 85 mg) or twice-daily Isentress (400 mg). In addition, participants took a Norvir (ritonavir)-boosted protease inhibitor plus another antiretroviral.

The most common background regimen was Norvir-boosted Prezista (darunavir) plus Viread (tenofovir). Participants who took Reyataz (atazanavir) or Kaletra (lopinavir/ritonavir) received a lower dose of elvitegravir, 85 mg daily instead of 150 mg.

After 96 weeks, 48 percent of patients in the elvitegravir group achieved and maintained viral loads (amount of HIV in the blood) of less than 50 copies per milliliter, compared to 45 percent of patients in the Isentress group.

Gilead reported that the rates and types of side effects were also comparable, and that discontinuation rates due to side effects were similar between the two groups.

The company had previously reported that, after 48 weeks, the most common side effects in participants taking elvitegravir were diarrhea (12 percent of participants), upper respiratory tract infection (6 percent), bronchitis (5 percent), back pain (5 percent), depression (5 percent), sinus infection (4 percent), joint pain (4 percent), nausea (4 percent), and urinary tract infection (3 percent).

Gilead stated that it would present the full clinical trial results at a scientific conference in 2012.

For more information, please see the Gilead Sciences press release.

Over a third of the HIV-positive women in the study had neuropathy. African-American women were about two thirds more likely to have neuropathy than women of other races.

“Why neuropathy is more prevalent [in African-American women] is unclear, and there is little data on any association between neuropathy and race  (not just HIV neuropathy),” said Dr. Yaacov Anziska, from the Department of Neurology at SUNY-Downstate Medical Center in Brooklyn, New York and lead author of the study.

“Clinicians and care providers should investigate for neuropathy in African-American women with HIV/AIDS. This entails both asking patients about pain, numbness, and tingling in their feet, as well as checking reflexes and sensation on clinical examination,” he added.

HIV-associated neuropathy is a nerve condition characterized by chronic pain in the hands and feet and sometimes the loss of sensation in the arms and legs.

Researchers estimate that the condition affects about half of all people with HIV. It can be caused by both HIV infection and by some HIV treatments, particularly the older nucleoside reverse transcriptase inhibitors (NRTIs) didanosine (Videx) and stavudine (Zerit).

According to the study authors, previous studies have linked low CD4 (white blood cell) counts, high viral loads (amount of HIV in the blood), diabetes, and older age with a higher risk of HIV-associated neuropathy. However, the effects of race and gender on risk of neuropathy have not been well studied.

The study included 973 HIV-positive women. Nine percent of the women were Caucasian, 64 percent were African-American, and 20 percent were Hispanic. Seventeen percent of the women had hepatitis C in addition to HIV, 21 percent had diabetes, and 17 percent were heavy alcohol users. The average age was 42 years old.

Results showed that 36 percent of the women had HIV-associated neuropathy; 21 percent of the women with neuropathy were Hispanic and 67 percent were African-American. By comparison, 31 percent and 53 percent of women without neuropathy were Hispanic and African-American, respectively.

In addition, 39 percent of women with HIV-associated neuropathy had hepatitis C, compared to 22 percent of HIV-positive women without neuropathy. Over 26 percent of women with neuropathy were diabetic, compared to 16 percent of HIV-positive women without neuropathy.

Overall, the researchers calculated that HIV-positive women with hepatitis C or diabetes were about 1.4 times more likely to have HIV-associated neuropathy than HIV-positive women without these conditions. In addition, older age was linked to a 30 percent higher risk of HIV-associated neuropathy, and African-American race with a 67 percent higher risk.

The researchers found that there was no significant effect of alcohol use on risk of neuropathy. They also found, contrary to previous studies, that height, CD4 cell counts, viral loads, or use of older NRTIs such as didanosine and stavudine had no effect on risk of neuropathy in this study.

They speculated that this was due to a shorter average height, relatively high CD4 counts, and minimal use of older NRTIs by the women who participated in the study.

For more information, please see the study in the Journal of the Neurological Sciences (abstract).

The study authors noted that the decrease in life expectancy for HIV-positive men is comparable to the effect of cigarette smoking or having a chronic disease like diabetes.

“Men who have sex with men who are recently infected are estimated to have a good life expectancy, provided they are diagnosed early (and have good access to HIV care),” said Fumiyo Nakagawa, a researcher at UCL Medical School in London and lead author of the study.

“Our model has also estimated that life expectancy is further prolonged if the individual does not smoke, does not interrupt treatment, and has good adherence to treatment,” she added.

Life expectancy refers to the expected number of years of life remaining for an individual at a given age. In the general population, several factors, including sex, race, and lifestyle habits, are known to influence life expectancy. Various factors, like better drugs, earlier detection, and increased experience of physicians in treating HIV, are thought to contribute to increased life expectancy of people with HIV.

A Danish study published earlier this year found that HIV-positive individuals suffer from higher death rates mainly due to HIV and non-HIV related risk factors such as poor response to antiretroviral therapy, co-infection with hepatitis C or other diseases, and drug and alcohol abuse.

According to the study authors, most studies so far have based life expectancy estimates on current death rates in people with HIV. Since drugs’ ability to suppress the amount of HIV in the blood have improved over time, and since therapy benefits on death rates may take years to fully take effect due to slow increases in CD4 (white blood cell) counts, life expectancy for HIV-positive people may have been underestimated.

In this study, researchers used a computer simulation model of HIV infection and the effects of antiretroviral therapy to estimate life expectancy for a man who has sex with men and who becomes HIV positive in 2010 at the age of 30 years old. They also attempted to determine how life expectancy varied depending on how early or late HIV was diagnosed. For comparison, the researchers used general population death rates for men in the United Kingdom for 2009.

The model assumed that a man with HIV would start a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, then switch to a boosted protease inhibitor-based regimen in the case of virologic failure.

The likelihood of treatment interruption was assumed to be 1.5 times higher in individuals with lower treatment adherence. Based on results from previous studies, a 1.5-fold increase in risk for all non-AIDS deaths was assumed for men with HIV throughout life.

Researchers also assumed a 40 percent chance of being a smoker and no hepatitis C co-infection.

Results showed that in a society with a high rate of HIV diagnosis, in which HIV was likely to be diagnosed soon after infection, the median age of death was estimated to be 75 years old. Risk of death within five and 10 years after infection was 2.3 percent and 5.2 percent, respectively. In addition, 57 percent, 78 percent, and 97 percent of men were diagnosed by three, five, and 10 years after infection, respectively.

Under this model, the median time from infection to diagnosis was 2.8 years, and the median CD4 cell count at diagnosis was 432 cells per microliter. In addition, the average time from infection to starting antiretroviral therapy was almost six years. Individuals were estimated to spend an average of 39 years on treatment, of which all but roughly seven years were spent actually receiving antiretroviral therapy (as opposed to periods of interrupted treatment).

The chance of treatment interruption at least once during an individual’s lifetime was estimated at 85 percent. Estimated life expectancy increased by 1.5 years when it was assumed that no treatment interruptions occurred.

It was estimated that 41 percent of individuals will at some stage progress to AIDS. However, only 14 percent of deaths were predicted to be from AIDS-related illnesses, and only 10 percent of men predicted to die of AIDS were also predicted to have resistance to all three major antiretroviral drug classes (nucleoside-reverse transcriptase inhibitors, NNRTIs, and protease inhibitors) plus integrase inhibitors.

Results also showed that in a society with a low HIV diagnosis rate, in which HIV was diagnosed only when symptoms were present, life expectancy for HIV-positive men who have sex with men was 71.5 years, indicating that an average of 10.5 years of life were lost compared to people without HIV.

With a low diagnosis rate, the median CD4 count was 140 cells per microliter at diagnosis; 22 percent, 37 percent, and 74 percent of individuals were diagnosed with HIV within three, five, and 10 years after infection, respectively. Consequently, there was a higher risk of death within 10 years after diagnosis (13 percent compared to 5.2 percent with a high diagnosis rate).

However, the effect of late diagnosis on life expectancy after this time was less significant due to the long-lasting effects of antiretroviral therapy, even in those who start treatment when CD4 cell counts are low.

The researchers estimated that the effect of late diagnosis would be greatest in the first 15 to 20 years after infection. Late diagnoses also increased the probability of transmitting HIV to others because lack of treatment increases risk of HIV transmission.

For more information, please see the study in the journal AIDS (abstract).

However, the study authors also found that greater viral loads may predict decreased treatment efficacy.

Based on their results, the authors stated that plans for radiation therapy and the prescribed doses used do not necessarily need to be altered for HIV-positive men with prostate cancer.

In men, prostate cancer is the third most common cause of death from cancer; in men over the age of 75 it is the most common cause of death from cancer.

As the life expectancy of people with HIV rises, diagnosis and treatment of prostate cancer in HIV-positive men will become increasingly important.

In this study, researchers examined the safety and efficacy of external-beam radiotherapy (EBRT) for prostate cancer in HIV-positive men compared with HIV-negative men. EBRT is the most common form of radiotherapy and involves an external source of radiation that is pointed at the tumor, in this case within the prostate.

The researchers retrospectively analyzed the medical records of 13 HIV-positive men with prostate cancer and 26 HIV-negative men with prostate cancer. Patients were followed for a median of 39 months.

The average age for the HIV-positive group was 55 years old compared with 60 years old for the HIV-negative comparison group. Most patients (77 percent) were African American.

Sixty-two percent of the HIV-positive men in the study were receiving highly active antiretroviral therapy (HAART) at the time of diagnosis with prostate cancer. In addition, one patient started HAART just before beginning radiation therapy.

Most patients (77 percent) received radiation specifically to the prostate. The rest received radiation to the entire pelvis.

Results showed that the 4-year biochemical failure-free survival rate – as shown by stable prostate-specific antigen levels, a protein thought to be a marker of prostate cancer – was 87 percent in HIV-positive patients and 89 percent in control group patients. The difference in survival between the two groups was not statistically significant.

Overall, 23 percent of the HIV-positive men experienced a biochemical failure compared with 12 percent of HIV-negative patients; this difference was also not statistically significant. None of the HIV-positive men died during the course of the study.

Higher viral loads (amount of HIV in the blood) before and after radiation therapy were associated with increased risk of biochemical failure.

Results also showed that patients with HIV were less likely to experience side effects from radiation therapy. Nearly half (46 percent) of HIV-positive patients experienced no acute side effects of the reproductive and urinary systems or the stomach and intestines, compared to 4 percent to 8 percent of HIV-negative men.

However, due to the small size of the study and its retrospective nature, the researchers noted that it cannot be concluded that HIV-positive people have higher tolerance for radiation therapy.

Results also showed that CD4 (white blood cell) counts decreased following radiation therapy for 85 percent of the HIV-positive patients. In addition, 54 percent of the patients with HIV experienced an increase in viral load following radiation therapy.

The average decrease in CD4 counts for HIV-positive patients was 193 cells per microliter. The average increase in viral loads was about 6,800 copies per milliliter.

HIV-positive patients receiving whole-pelvis radiation experienced similar declines in CD4 cell counts as patients receiving radiation directed at the prostate only. The researchers suggested that a stress response to radiation therapy may account for the decline in CD4 cell counts.

Declines in CD4 counts were not permanent, and no patients had HIV-related complications or opportunistic infections during follow-up that were related to radiation therapy.

For more information, please see the study in the International Journal of Radiation Oncology∙Biology∙Physics (abstract).

The results suggest that effects of early treatment on the size of the latent HIV reservoir, and therefore the viral setpoint, may only be temporary. They also suggest that reinitiating therapy in early treated patients should not be delayed too long.

“Early treatment during primary HIV infection may create a window of opportunity for (future) interventions aiming at eradicating HIV,” said Dr. Viktor von Wyl and Dr. Huldrych Günthard, from the Division of Infectious Diseases and Hospital Epidemiology at the University Hospital in Zürich, Switzerland, and lead authors of the study.

“It is plausible and likely that a smaller viral reservoir will increase chances for success of such (still experimental) interventions. However, it is conceivable that such therapeutic strategies might be much more successful if applied in patients with a viral reservoir of reduced size. Thus, to know that the viral reservoir can be lowered by early intervention is of great value,” said Dr. von Wyl and Dr. Günthard.

“Nevertheless, the limited and waning positive effect on the viral setpoint should also act as a warning signal to physicians when considering stopping therapy outside of study protocols,” they added.

During the early stages of HIV infection, HIV replicates rapidly and many immune cells are infected with the virus. This “acute” stage, also called primary infection, usually lasts several weeks to a few months. After that, the chronic stage of HIV infection begins, which can last years or even decades. At this point, the viral load (amount of HIV in the blood) naturally levels off; this level is called the setpoint.

When a person with HIV starts antiretroviral therapy – often during the chronic phase of HIV infection – the amount of HIV circulating in the blood usually drops to undetectable levels. However, some cells remain infected with latent HIV – HIV that lies dormant and will start multiplying again until the viral setpoint is reached if antiretroviral therapy is stopped. Current antiretrovirals cannot get rid of latent HIV.

Some previous research, including research by the same study authors, has suggested that antiretroviral therapy initiated in the acute phase of HIV infection may help limit the size of this latent reservoir (see related AIDS Beacon news) and lower the viral setpoint. However, results have been conflicting, and according to the study authors, little is known about the long-term effects of antiretroviral therapy on the viral load setpoint and the size of the latent HIV reservoir after early treatment is stopped.

In this study, the Swiss researchers examined viral load and HIV DNA levels, an indicator of the size of the latent HIV reservoir, before, during, and after treatment in people with HIV who started therapy within four months of initial HIV infection.

The study included 67 HIV-positive adults who started treatment early; 33 of these participants (49 percent) subsequently chose to stop therapy after one year of detectable viral loads. The study also included a comparison group of 79 untreated patients with chronic HIV.

Participants who started treatment early and then chose to stop were followed for a median of 37 months after stopping treatment. The comparison group of untreated participants was followed for a median of 34 months.

Results showed that HIV viral loads were very high in most patients before starting treatment. During antiretroviral therapy, viral loads decreased rapidly to undetectable levels but the drop in HIV DNA levels was significantly slower. In addition, HIV DNA levels remained constant after about 12 months of therapy, indicating that antiretroviral therapy was ineffective at eliminating residual latent HIV even when started early.

After stopping treatment, results showed that both viral loads and HIV DNA increased rapidly, then leveled off after about nine months. Participants who started treatment early had significantly lower viral loads than participants who were not treated.

However, three years after stopping treatment, participants in the early treatment group no longer had lower viral loads than participants who were not treated, indicating that the effects of early treatment on the viral setpoint were only temporary.

Results also showed that duration of antiretroviral therapy, pre-treatment HIV DNA levels, and CD4 (white blood cell) counts had no significant effect on post-treatment viral loads. Only the timing of treatment was significant: patients who began treatment 60 days or less after infection tended to have lower post-treatment viral loads than patients who started therapy between 61 and 120 days after infection.

For more information, please see the study in PLoS One.

“Antiretroviral therapy taken during pregnancy is not detrimental to bone development and bone health of the fetus/infant. Due to the awareness about the numerous side effects of antiretrovirals, we wanted to verify the safety for the fetus of the therapy,” said Dr. Stefano Mora from the Laboratory of Pediatric Endocrinology at the San Raffaele Scientific Institute of Milan, Italy, and lead author of the study.

“In simple words, HIV-infected mothers should take their therapy and do not have to worry about the bone health of their children,” he added.

Antiretroviral therapy during pregnancy is important for preventing mother-to-child transmission of HIV. However, according to the study authors, antiretrovirals have been linked to decreased bone mass and altered bone metabolism in HIV-positive children and adolescents.

Viread (tenofovir), which is also a component of Truvada (emtricitabine/tenofovir), has been particularly linked to bone loss in HIV-positive children and adults (see related AIDS Beacon news).

In this study, the researchers investigated the effect of antiretroviral drug exposure during pregnancy on newborns and infants.

The study included 38 infants who were exposed to antiretrovirals during pregnancy. The infants were born between 35 and 39 weeks of gestation. For comparison, the study also included 94 newborns with HIV-negative mothers, born between 37 and 40 weeks of gestation.

More than half (58 percent) of the HIV-positive mothers were taking two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor, and a quarter (24 percent) were taking two NRTIs and one non-nucleoside reverse transcriptase inhibitor.

The mothers received one of the following NRTI backbones: Epivir (lamivudine) plus zidovudine (Retrovir), Epzicom (abacavir/lamivudine), Epivir plus didanosine (Videx), or Truvada.

The median length of infant exposure to antiretrovirals during pregnancy was 14 weeks. All mothers had cesarean sections, and all newborns received antiretroviral therapy and were formula fed to avoid mother-to-child HIV transmission.

Measurements of bone development were obtained as soon as possible after birth and prior to hospital discharge. Further measurements were taken at follow-up visits four and 12 months after birth.

Results showed that antiretroviral-exposed infants had lower weight and length measurements at the beginning of the study and at their four-months follow-up visit, due to shorter gestation times compared to unexposed infants. However, these differences were no longer significant at age 12 months.

Ultrasound measurements of the shinbones of exposed and unexposed infants showed that there was no difference in bone quality or maturation between the two groups. Results also showed that bone formation and bone break down or loss (bone resorption) rates did not differ between the two groups.

A separate analysis showed that there were no significant differences in bone development in infants exposed to Viread or Truvada; however, the researchers noted that further studies are needed to confirm this observation.

For more information, please see the study in the journal Bone (abstract).

“With the advent of highly active antiretroviral therapy, [non-HIV-related] infections are becoming a more common reason for people with HIV to be admitted to intensive care units. However, we know little about the types of infections these patients are most at risk for and the factors that affect patient outcomes,” said Dr. Jared Greenberg of the Department of Medicine at Emory University and lead author of the study.

“The patients in our study had frequent exposure to hospitals and other healthcare settings. The majority of the infections requiring intensive care unit stay were likely associated with this exposure. We suggest that further research and resources should focus on preventing and treating these types of infections,” added Dr. Greenberg.

The results also showed that patients with health-care associated or AIDS-related infections tended to have lower CD4 (white blood cell) counts and were less likely to be on highly active antiretroviral therapy (HAART) than patients with community-acquired infections.

Based on their results, the authors suggested that studies be conducted on the effects of starting HAART immediately in HIV-positive sepsis patients.

“It is important for physicians to understand that care for critically ill patients with HIV should not be deemed futile even if their patients are severely immunosuppressed,” said Dr. Greenberg.

Health care-associated infections are infections acquired due to admission to a hospital or other health care setting, such as a nursing home. Community-acquired infections are those that occur in patients who are not in a health care setting at the time of infection and are not considered AIDS-related.

According to the study authors, people with HIV are thought to be at greater risk for acquiring health care-related infections because of weakened immune systems, frequent treatment with antibiotics, and frequent invasive operations.

In this retrospective study, researchers sought to determine the sources of infections in HIV-positive patients who were admitted to hospital intensive care units with sepsis.

Sepsis, also known as blood poisoning, is a severe illness in which bacteria or other disease-causing organisms spread to the bloodstream and overwhelm the immune system, potentially leading to organ failure and death.

The researchers also attempted to determine which factors, such as HAART use or CD4 counts, might affect patient outcomes.

The study included 125 HIV-positive patients who were admitted to intensive care units in Atlanta between October 2006 and January 2009 with severe sepsis. A majority (65 percent) was male and most (85 percent) were African-American. The median CD4 cell count was 30 cells per microliter.

Twenty-two percent of patients were on HAART prior to hospitalization. Eleven percent of the patients were diagnosed with HIV during their time in the intensive care unit, and 12 percent were started on HAART during hospitalization.

Results showed that 58 percent of sepsis-causing infections were health care-associated infections, 28 percent were AIDS-related, and 14 percent were community-acquired infections.

The death rate for participants was 42 percent. The disease severity and risk of death was similar across all three infection types.

The most common kind of community-acquired infection was bacterial pneumonia. Pneumocystis pneumonia, a fungal lung infection, comprised 51 percent of AIDS-related infections. Patients with health care-associated infections had a variety of infection types, including both bacterial and fungal infections.

The most common infections were respiratory, bloodstream, and central nervous system infections.

Results also showed that risk of death was related to infection severity but not CD4 count or HAART use. Since only 18 percent of patients had undetectable viral loads (amount of HIV in the blood), the relationship between undetectable viral load and survival was not determined.

On average, patients with both health care-associated and AIDS-related infections had lower CD4 counts than patients with one type of infection only.

For more information, please see the study in the Journal of Critical Care (abstract).

The study authors also noted that participants with the most severe limb fat loss had the largest gain in limb fat after switching.

“This is good news for participants with severe loss of limb fat, as switching treatment can positively change their body image,” said Allison Humphries, Senior Clinical Project Coordinator at the Kirby Institute of the University of New South Wales, Australia and the lead author of the study.

“We are currently finalizing a publication looking at the changes in bone markers for the same study. This is to assess the effect of switching to Epzicom or Truvada on bone mineral density,” added Humphries.

Lipodystrophy is characterized by abnormal body fat redistribution, such as loss of fat from the arms and legs and build-up of fat in the abdomen. People with lipodystrophy also commonly suffer from metabolic syndrome, which is a syndrome that includes insulin resistance, high cholesterol levels, high blood pressure, and higher risk for type 2 diabetes and heart attacks.

Lipodystrophy and metabolic syndrome are common side effects of certain antiretrovirals. In particular, protease inhibitors and older nucleoside reverse transcriptase inhibitors (NRTIs), such as zidovudine (Retrovir), stavudine (Zerit), and didanosine (Videx), are linked with significant body fat redistribution and metabolic changes.

Previous research has shown that lipodystrophy can result in serious psychological problems and stigma, eventually leading to treatment non-adherence.

According to the study authors, changing therapy from older NRTIs to newer ones such as Ziagen (abacavir) or Viread (tenofovir) has been shown to help with the gradual recovery of fat that was lost due to treatment in people with HIV, particularly in those with severe cases of lipoatrophy (fat loss in the arms and legs).

In this prospective study, the investigators examined factors that might predict changes in the amount and distribution of limb fat (fat in the arms or legs) in people who switched from older NRTIs to Truvada (emtricitabine/tenofovir) or Epzicom (abacavir/lamivudine).

The study included 303 participants on antiretroviral therapy who had undetectable viral loads (amount of HIV virus in the blood). The average participant age was 45 years old. Most participants were male (98 percent) and Caucasian (86 percent). The average length of HIV infection was 10 years.

Study participants were randomly assigned to switch to either Truvada or Epzicom. Researchers then monitored their body fat levels and other factors such as cholesterol and blood glucose levels over a period of 96 weeks.

Results showed that patients in both treatment groups had an average increase in limb fat of 7 percent by week 48 and 13 percent by week 96. However, these gains were considered clinically moderate, meaning that patients were still classified as having lipoatrophy.

Overall, 51 percent of patients experienced a 10 percent or greater gain in limb fat during the study, and 35 percent had a 20 percent or greater gain in limb fat. However, 34 percent of participants had no significant gain in limb fat by the end of the study period.

There was no significant difference in the amount of fat gained by participants in the Truvada group versus the Epzicom group.

The results also showed that greater gains in limb fat were associated with more severe limb fat loss prior to starting the study. In addition, participants with the greatest increases in limb fat were more likely to be taking zidovudine, stavudine, or didanosine treatment regimens immediately before starting the study. They also had higher fasting blood glucose levels and higher levels of interleukin 6, an inflammatory protein associated with diabetes and other metabolic diseases, prior to the change in treatment.

For more information, please see the study in PLoS One.

Most (84 percent) of the children in the study who did not survive were born before 1994, at least three years before highly active antiretroviral therapy (HAART) became widely available.

“As antiretroviral utilization milestones were achieved throughout the course of this study, in going from single-agent to dual-agent and then to triple-agent therapy (Highly Active Antiretroviral Therapy – HAART), there have been dramatic parallel improvements in mortality rates among the cohort resulting in prolonged overall survival,” said Dr. Bill Kapogiannis, program director of the Adolescent Medicine Trials Network for HIV/AIDS Interventions and lead author of the study.

However, the study authors noted that despite the large reductions in death rates, the average annual death rate of HIV-positive children during the HAART era remained 50-fold higher than the death rate of HIV-negative children of the same age during the same period in the United States.

They hypothesized that this may be due to increased susceptibility to death from other causes besides HIV, such as non-AIDS-defining infections.

“During this period, as deaths associated with opportunistic infections declined, the numbers of deaths not associated with these infections remain and thus, become more prominent,” said Dr. Kapogiannis.

HAART is defined as therapy involving at least three antiretroviral drugs, usually two nucleoside reverse transcriptase inhibitors combined with either a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, or an integrase inhibitor.

Since the introduction of HAART during the mid- to late-1990s, the frequency of deaths in adults and children with HIV has decreased considerably.

According to the study authors, while trends in survival and death among HIV-positive children have been examined in previous clinical trials, these trials have enrolled patients anytime from birth throughout childhood. As a result, deaths early on when children are particularly susceptible to infections might have been overlooked.

In this study, investigators compared death rates from birth in HIV-positive children born between 1986 and 2004. In particular, the researchers examined three time periods: the no antiretroviral therapy/monotherapy period from 1986 through 1990, the monotherapy/dual therapy period from 1991 through 1996, and the HAART period from 1997 through 2004.

The multicenter, retrospective study included HIV-positive pregnant women and their newborns in four cities in the U.S.: New York, Atlanta, Baltimore, and Newark, NJ. A total of 364 HIV-positive children were included in the study.

Results showed that the death rates of children in the first period and the second period were six and two times higher, respectively, than the death rate of children in the HAART era. However, the death rate in the HAART era remained 50 times higher than that of HIV-negative children of the same age.

The six-year survival rates for children born in the three eras were 57 percent, 76 percent, and 91 percent, respectively.

In addition, the 10-year survival rate for children who received HAART at any age was 94 percent, compared to 45 percent for children who did not receive HAART.

Eighty-one percent of deaths in the study occurred in children aged 3 years or less, and 61 percent of deaths occurred in children aged 2 years or less.

Results also showed that the percentage of deaths due to opportunistic infections declined over time, from 32 percent in 1986 to 1990, to 17 percent in 1991 to 1996, to 9 percent in 1997 to 2004.

The three most common causes of death in the study were end-stage AIDS (24 percent), opportunistic infections (19 percent), and pneumonia (15 percent).

Children who died were more likely to be born in the late 1980s or early 1990s, have a birth weight of less than 5.5 pounds (2.5 kg), be born prematurely (less than 37 weeks), or have low weight or height for their age at three months old. Children with thymic dysfunction, children who were infected with HIV before birth, and children who had not received zidovudine (Retrovir) during and before birth to prevent HIV infection were also at greater risk of death.

HIV transmission from mother-to-child before birth was associated with greater risk of death compared with HIV transmission during labor and delivery; however, the effect was only significant until two years of age.

For more information, please see the study in the Journal of Clinical Infectious Diseases.

“The most important message from the study is that dolutegravir is a safe and highly potent drug which can be given at low doses without a pharmacologic booster once daily,”  said Dr. Jan van Lunzen, a professor at the University Medical Center Hamburg-Eppendorf, in Hamburg, Germany and lead author of the study.

“Thus it has the potential to be a very attractive future component of combination antiretroviral therapy, both in antiretroviral-naïve as well as experienced patients,” he added.

Patients receiving dolutegravir also showed a more rapid decrease in viral load (amount of HIV in the blood) compared to patients receiving Sustiva. The decrease was maintained through week 48 of the study, and the rate of decrease was similar to that reported for the integrase inhibitor Isentress.

The investigators noted that this might have important implications for people with HIV who require an especially rapid reduction in viral load, for example, late-presenting pregnant women with HIV.

The investigators stated that based on their results, they selected the once-daily 50 mg dose of dolutegravir, the highest well-tolerated dose studied, for further testing in Phase 3 trials.

“Currently there are three Phase 3 studies underway in treatment-naïve populations comparing dolutegravir with either efavirenz [Sustiva], darunavir/r [Norvir-boosted Prezista], or raltegravir [Isentress]. Another Phase 3 trial is currently ongoing in experienced patients with previous treatment failure,” said Dr. van Lunzen.

The interim results after 48 weeks were first presented at the 6^th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (see related AIDS Beacon news),

Dolutegravir (S/GSK1349572) is a potential new integrase inhibitor being developed by ViiV Healthcare, a joint venture by GlaxoSmithKline and Pfizer.

Currently, the only approved integrase inhibitor is Isentress (raltegravir), which is marketed by the United States pharmaceutical company Merck. Isentress must be taken twice-daily in combination with other antiretrovirals as part of highly active antiretroviral therapy.

In recent years, the U.S. Food and Drug Administration has approved once-daily rather than twice-daily dosages of several antiretrovirals. Previous research has shown that once-daily dosing is more convenient and promotes better adherence to drug regimens. Better adherence allows for slower disease progression and helps prevent the development of drug-resistant HIV strains.

However, results from a recent study showed that Isentress once daily is not as effective as twice daily (see related AIDS Beacon news). Elvitegravir, which is another investigational integrase inhibitor that is currently in Phase 3 clinical trials, is given once daily but must be taken with a booster such as Norvir (ritonavir) or cobicistat.

According to the study authors, previous studies of dolutegravir in people have shown it to be long lasting without the need for a booster. Results of another ongoing study also indicate that dolutegravir is effective against viral strains resistant to both Isentress and elvitegravir.

The 96 week-long Phase 2 trial was designed to test the safety and efficacy of several once-daily dolutegravir dosages relative to Sustiva (efavirenz). Sustiva, when combined with Truvada (emtricitabine/tenofovir) in the form of Atripla (efavirenz/emtricitabine/tenofovir), is the most commonly prescribed first-line regimen to treat HIV.

A total of 205 previously untreated HIV-positive adults were randomly assigned to receive 10 mg, 25 mg, or 50 mg dolutegravir, or 600 mg Sustiva. Patients in each group also took either Truvada or Epzicom (abacavir/lamivudine).

Results showed that after 16 weeks, about 93 percent of patients in all dosage groups of dolutegravir had undetectable viral loads, with little difference between the dose groups. Sixty percent of participants taking Sustiva had undetectable viral loads.

After 48 weeks, 91 percent, 88 percent, and 90 percent of participants in the dolutegravir groups, respectively, and 82 percent of the participants in the Sustiva group had successfully achieved undetectable viral loads.

In addition, CD4 (white blood cell) counts increased in all three dolutegravir groups and in the Sustiva group through week 48. Average increases were larger in the dolutegravir group, 231 cells per microliter versus 174 cells per microliter in the Sustiva group.

Nearly half of participants (46 percent) experienced one or more drug-related side effects during the first 48 weeks of the study, but investigators concluded that no serious side effects were related to dolutegravir. More participants in the Sustiva group had moderate or severe drug-related side effects (20 percent, compared with 8 percent in the dolutegravir groups).

The most common side effects in participants taking dolutegravir were nausea (12 percent of participants), diarrhea (8 percent), headache (6 percent), dizziness (3 percent), fatigue (3 percent), and weakness (3 percent).

Six participants withdrew from the study: one each in the 25 mg and 50 mg dolutegravir groups due to upset stomach/indigestion and lymphatic cancer, respectively, and four in the Sustiva group due to drug intolerance, drug sensitivity, abnormal dreams, and suicide attempt.

Investigators did not identify any HIV integrase mutations in patients in the study.

For more information, please see the study in The Lancet Infectious Diseases (abstract).

“[Patients] could use elvitegravir [once daily] instead of Isentress [twice daily] in combination with a boosted protease inhibitor with the same efficacy and safety,” said Dr. Jean-Michel Molina, a researcher at the Hôpital Saint Louis and University of Paris and lead author of the study.

The study authors noted that once daily dosing as opposed to twice daily dosing might improve patients’ adherence to treatment.

Investigators previously presented the results of the study in July at the International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (see related AIDS Beacon news).

Elvitegravir, which is being developed by Gilead Sciences, and Isentress (raltegravir) are both integrase inhibitors, a relatively new class of antiretroviral. Currently, Isentress is the only approved integrase inhibitor.

In this clinical trial, researchers compared the safety and efficacy of elvitegravir to that of Isentress in 702 HIV-positive adults who had previously been treated for HIV. Two-thirds of the participants had resistance to two or more classes of antiretroviral drugs.

Half of the participants were randomly assigned to receive elvitegravir once daily and the other half Isentress twice daily. Placebo pills were used to ensure that all participants received the same number of pills daily.

All patients also took a Norvir (ritonavir)-boosted protease inhibitor and a third antiretroviral, which was either a nucleoside reverse transcriptase inhibitor, Intelence (etravirine), Selzentry (maraviroc), or Fuzeon (enfuvirtide). The most commonly used protease inhibitor was Prezista (darunavir).

Results showed that after 48 weeks, 59 percent of patients in the elvitegravir group achieved and maintained undetectable viral loads (amount of HIV in the blood), compared to 58 percent of patients in the Isentress group.

Increases in CD4 (white blood cell) counts were also similar between the two groups: an average increase of 119 of cells per microliter in participants taking elvitegravir versus 127 cells per microliter in participants taking Isentress.

Drug adherence up to week 48 of the study was determined by pill counts at every visit during the study. Adherence was similar (95 percent) in both groups.

Rates and types of side effects were similar between the two groups. The most common side effects in participants taking elvitegravir were diarrhea (12 percent of participants), upper respiratory tract infection (6 percent), bronchitis (5 percent), back pain (5 percent), depression (5 percent), sinus infection (4 percent), joint pain (4 percent), nausea (4 percent), and urinary tract infection (3 percent).

Although diarrhea was equally common in both treatment groups in the first month of treatment, diarrhea was reported more often after the first month by patients receiving elvitegravir.

One percent of patients assigned to elvitegravir experienced serious side effects, compared to two percent of patients assigned to Isentress. Two patients (0.5 percent) and eight patients (2 percent) died in each group, respectively, during the study period.

The trial will continue for an additional 48 weeks. In addition, studies are ongoing of elvitegravir as a component of the investigational single-tablet combination “Quad” (cobicistat/elvitegravir/emtricitabine/tenofovir) regimen in previously untreated HIV-positive adults.

Gilead stated in July that it plans to apply for approval of elvitegravir in the U.S. and Europe in 2012.

For more information, please see the study in The Lancet Infectious Diseases (abstract).

“We are encouraged by these interim results with Victrelis in combination therapy in this difficult-to-treat patient population,” said Dr. Roger Pomerantz, senior vice president of Infectious Diseases at U.S. pharmaceutical company Merck, in a press release.

Based on the results, Dr. Pomerantz said that Merck is planning to initiate a Phase 3 study of Victrelis in people with both HIV and hepatitis C later this year.

The results were presented last week at the Infectious Diseases Society of America 2011 Annual Meeting in Boston.

Hepatitis C is a liver disease caused by the hepatitis C virus. If untreated, infection with the hepatitis C virus can cause damage and scarring to the liver, liver cancer, and eventually liver failure. Once the liver fails, a liver transplant is necessary for a patient to survive. Some people who are infected can spontaneously clear the virus themselves; the rest need treatment with antiviral drugs.

HIV patients with hepatitis C are less likely to clear the infection compared to patients with hepatitis C only. Once the infection develops and becomes chronic, HIV patients are less likely to respond to hepatitis C treatment, which currently consists of peginterferon-alfa  (PegIntron, Pegasys) plus ribavirin (Rebetol, Copegus) for 48 weeks.

Victrelis (boceprevir) was approved by the United States Food and Drug Administration in May of this year for the treatment of hepatitis C, in combination with peginterferon-alfa and ribavirin. However, it was not approved at the time for people with both HIV and hepatitis C, due to lack of information on efficacy in people who are co-infected.

In this ongoing Phase 2 study, researchers are comparing the efficacy of Victrelis plus PegIntron (peginterferon alfa-2b) and ribavirin to PegIntron and ribavirin alone in adult patients with both hepatitis C and HIV.

The study includes 98 participants who were randomly assigned to receive one of the two above mentioned treatments. All participants had stable HIV infections, were receiving an optimized antiretroviral regimen, and had not previously been treated for hepatitis C.

Since studies have shown that certain HIV antiretrovirals may potentially interact with Victrelis, non-nucleoside reverse transcriptase inhibitors, zidovudine (Retrovir), stavudine (Zerit), and didanosine (Videx) were not allowed during the study.

Most participants were Caucasian (82 percent), and a majority were male (69 percent). The median participant age was 43 years old.

Participants in each of the two treatment groups received four weeks of treatment with PegIntron plus ribavirin. Two-thirds of the participants then initiated treatment with Victrelis three times daily in addition to PegIntron and ribavirin; the remaining participants continued treatment with just PegIntron plus ribavirin.

Results showed that after 24 weeks, 70 percent of participants taking Victrelis had undetectable hepatitis C virus levels, compared to 34 percent of participants taking PegIntron and ribavirin alone.

The most common side effects in the group receiving Victrelis versus the group receiving PegIntron and ribavirin alone were: low white blood cell levels (neutropenia), 13 percent versus 3 percent; bad taste in the mouth, 25 percent versus 15 percent; vomiting, 25 percent versus 15 percent; fever, 34 percent versus 21 percent; headache, 28 percent versus 12 percent; and decreased appetite, 30 percent versus 18 percent.

Serious side effects occurred in 8 percent of the patients receiving Victrelis in combination with PegIntron and ribavirin, compared with 21 percent of patients receiving PegIntron plus ribavirin alone.

Overall, 14 percent of participants receiving Victrelis discontinued treatment due to side effects, compared to 9 percent of participants receiving PegIntron and ribavirin alone.

The trial will continue for an additional 24 weeks. Merck stated that final results are expected in 2012.

For more information, please see the study (abstract) or the Merck press release.

The results might help explain why highly active antiretroviral therapy is not always effective in treating some HIV-associated neurological problems, since these cells live longer than the more typical immune cells infected by HIV. The results also might allow physicians to predict who is at greatest risk for HIV-associated dementia.

“Our goal is to determine if there are biological markers in the cerebrospinal fluid of people [before they develop] HIV-associated dementia that predict current and/or continued neurological disease,” said Professor Ronald Swanstrom, a professor at the University of North Carolina School of Medicine and senior author of the study, in correspondence with The AIDS Beacon.

HIV-associated dementia is a severe neurological disease that develops when the HIV virus infects the central nervous system. Although the introduction of highly active antiretroviral therapy (HAART) has reduced the rate of HIV-associated dementia, HAART is not always effective in treating less severe HIV-associated neurological problems.

Results from a prior study by the same authors showed that the amount of HIV virus in the cerebrospinal fluid, the clear fluid in the spaces inside and around the brain and spinal cord, dropped much more slowly in people with HIV-associated neurological problems after starting antiretroviral therapy, compared to people with HIV without neurological problems.

In this study, the researchers attempted to determine the reason for this slower decrease in people with HIV-associated neurological disorders.

The researchers examined cerebrospinal fluid samples from 11 HIV-positive adults starting antiretroviral therapy. Eight of the participants had HIV-associated dementia. Two of these participants also had cerebrospinal fluid samples available from before they developed dementia.

Results showed that participants with HIV-associated dementia had two different HIV virus types in the cerebrospinal fluid. One of these HIV virus types reproduced in relatively short-lived immune cells called T cells, like HIV usually does. The other type reproduced in macrophages, which are longer-lived white immune cells.

Further analysis showed that the macrophage-infecting HIV was more common in patients who showed a slow decrease in the amount of HIV in the cerebrospinal fluid after beginning antiretroviral therapy. In contrast, rapid reduction in the amount of HIV in the cerebrospinal fluid was associated with the HIV virus infecting T cells only.

The authors hypothesized that the slow decrease in people with macrophage-infecting HIV occurs because these macrophages live longer than T cells, so the virus persists longer after antiretroviral therapy is initiated.

Antiretrovirals do not kill infected immune cells; they prevent HIV from infecting new cells. This means that if infected cells take longer to die on their own, it will take longer for HIV levels to drop.

The researchers also examined the samples from the two participants whose cerebrospinal fluid had been collected before they developed dementia.

Results showed that one of the two had the macrophage-infecting HIV in their cerebrospinal fluid for up to two years before being diagnosed with dementia. The other participant did not have macrophage-infecting HIV before their dementia diagnosis but did at the time of diagnosis. This finding suggests that the macrophage-infecting HIV developed rapidly around the time the participant was diagnosed with HIV-associated dementia.

The researchers now want to test to see if having this type of HIV is a predictor of future HIV-associated dementia.

“We now have funding to look at virus in the cerebrospinal fluid of a group of people who are starting therapy with CD4 T cell counts below 300 cells per microliter,” said Professor Swanstrom.

“We want to know how often we see virus growing in the central nervous system in people without HIV-associated dementia and whether we can measure neurological impairment associated with localized infection in the cerebrospinal fluid,” he added.

For more information, please see the study in PLoS Pathogens.

The guidelines include updated information on initial combination regimens for previously untreated (treatment-naïve) people with HIV.

According to the guidelines, antiretroviral regimens may be classified as preferred regimens, alternative regimens, or acceptable regimens. Preferred regimens are recommended as the best treatment regimens for most people starting antiretroviral therapy.

Alternative regimens, while effective, have potential disadvantages when compared with preferred regimens. Acceptable regimens decrease the amount of HIV virus activity but lack data from large clinical trials on efficacy or might have greater side effects or potential for drug interactions.

The guidelines are intended for use by HIV care practitioners when treating HIV-positive adults and adolescents in the U.S. They were last updated in January.

Updates on antiretroviral initiation in HIV-positive people are summarized below.

Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Based Regimens

The updated guidelines list Edurant (rilpivirine) as an alternative NNRTI option for initial therapy in treatment-naïve patients (see related AIDS Beacon news). Edurant was approved by the U.S. Food and Drug Administration in May.

Information on Edurant has also been added to the guide’s tables on drug interactions, drug characteristics, and dosing recommendations for people with kidney or liver problems.

In addition, all Viramune (nevirapine)-based regimens have been reclassified in the updated guidelines as acceptable treatment options for patients beginning antiretroviral therapy. Previously, Viramune plus zidovudine/lamivudine (Combivir) was classified as an alternative regimen, while Viramune plus Epzicom (abacavir/lamivudine) and Viramune plus Truvada (emtricitabine/tenofovir) were classified as regimens that were acceptable but required caution when used.

Protease Inhibitor-Based Regimens

The updated guidelines now list Norvir (ritonavir)-boosted Prezista (darunavir) plus Epzicom as an alternative regimen. This regimen was previously listed as an acceptable regimen that required more data.

Regimens with unboosted Lexiva (fosamprenavir) are no longer listed as protease inhibitor options for treatment-naïve patients because these regimens are less effective than other protease inhibitor-based regimens. In addition, patients who experience virologic failure (failure of antiretrovirals to control HIV replication) while taking Lexiva may develop resistance to Prezista.

Isentress-Based Regimens

The new guidelines reclassify Isentress (raltegravir) plus Epzicom as an alternative regimen. The regimen was previously classified as acceptable but in need of additional data.

Dual-Nucleoside Reverse Transcriptase Inhibitor (NRTI) Options

The updated guidelines list zidovudine/lamivudine as an acceptable dual-NRTI option. This option was previously listed as an alternative option, but was reclassified because the combination is associated with greater side effects compared with Truvada and Epzicom and requires twice daily dosing. Zidovudine/lamivudine, however, is still the preferred dual-NRTI for pregnant women receiving antiretroviral therapy to avoid mother-to-child HIV transmission.

Didanosine (Videx) plus Epivir (lamivudine) is no longer listed as a dual-NRTI option for initial treatment because the combination has the least data from clinical trials and has more side effects compared with other dual-NRTI options.

In the updated guidelines, the authors point out that Ziagen (abacavir), which is also a component of Epzicom and Trizivir (zidovudine/lamivudine/abacavir), may increase the risk of heart attack; however, they note that this association is not definitive.

For more information, please see The Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents (pdf).

However, the researchers noted that the use of illegal drugs, which was more common in participants with hepatitis C and is linked to increased seizure risk, could have affected the study results. They suggested that studies of patients with hepatitis C only and hepatitis C patients without past illegal drug use would help determine the impact of the virus on the nervous system.

People with HIV and AIDS commonly experience neurological problems that can lead to a decline in brain function. Brain disorders in HIV-positive individuals, also referred to as HIV-associated neurocognitive disorders, are characterized by mental, behavioral, and movement disabilities and are associated with reduced survival.

Hepatitis C is a liver disease caused by the hepatitis C virus. If untreated, hepatitis C can cause damage and scarring to the liver, liver cancer, and ultimately liver failure. The disease affects around 30 percent of HIV-positive people. Co-infection is associated with faster hepatitis C disease progression and a higher mortality rate (see related AIDS Beacon news).

According to the study authors, research has suggested that hepatitis C virus may also affect the brain, and people with both HIV and hepatitis C may be at increased risk of brain problems.  However, the total rate of various brain disorders in HIV-positive individuals with hepatitis C is uncertain.

In this study, researchers attempted to determine the risk of brain disorders and death in people with both HIV and hepatitis C.

The study included 456 HIV-positive individuals who received treatment at two community clinics in Canada between 1998 and 2010.  Almost 20 percent of the participants had hepatitis C along with HIV; the rest had HIV alone.

The researchers measured the rates of HIV-related brain disorders and mood disorders like anxiety or depression. They also recorded drug-related muscular disorders, movement disorders including Parkinson’s disease, and opportunistic infections (infections that occur only in people with compromised immune systems) of the brain and spinal cord.

Most of the participants with HIV alone were homosexual men, while participants with both HIV and hepatitis C were more likely to be past injection drug users.

Results showed that the rate of multiple brain disorders was higher in HIV patients with hepatitis C, affecting 60 percent of co-infected participants versus 47 percent of participants with just HIV.

The researchers also found a higher mortality rate in people with both hepatitis C and HIV during the course of the study (24 percent of co-infected participants versus 14 percent of participants with HIV alone).

The study authors identified 58 different brain disorders among the study participants.  The most common disorder in both groups of HIV-positive patients was peripheral neuropathy (a condition that causes pain, numbness, burning, or tingling in the extremities); followed by HIV-associated dementia and minor neurocognitive disorder in individuals with HIV alone; and seizures or epilepsy in people with both HIV and hepatitis C.

Patients with HIV alone experienced only mild interference in their daily functioning due to brain disorders. However, most HIV-positive participants with hepatitis C were unable to continue working.

For more information, please see the study in the Journal of the Neurological Sciences (abstract).

Based on their results, the authors emphasized the need to counsel women about the possible increase in HIV risk with hormonal contraceptive use, especially the shot Depo-Provera, and the importance of condom use to decrease risk of HIV.

“Women should be counseled about potentially increased risk of HIV acquisition and transmission with hormonal contraception, particularly injectable methods, and about the importance of dual protection with condoms to decrease HIV risk,” said Renee Heffron, a researcher at the International Clinical Research Center at the University of Washington and lead author of the study, in a press release.

The researchers advocated further studies of other hormonal contraceptives, such as implants or patches, to determine whether they also affect HIV acquisition and transmission risk. They also argued that contraceptive counseling should be combined with HIV counseling and testing.

The results were first presented in July at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Rome.

According to the study authors, the prevention of unintended pregnancy in women with or at risk for HIV has benefits that include reduced mother-to-child transmission of HIV and improved health of children through spacing of pregnancies.

Many women throughout the world use hormonal birth control, which includes birth control pills and injected contraceptives such as Depo-Provera (depot medroxyprogesterone acetate). However, the effects of hormonal contraception on HIV risk are unclear; according to the authors, some studies have investigated the association between hormonal birth control and the risk of HIV acquisition and transmission but results have been conflicting.

In this study, researchers followed nearly 3,800 serodiscordant couples in seven African countries from 2004 to 2010. Serodiscordant couples are couples in which one partner is HIV-positive and the other partner is HIV-negative.  In most of the couples in this study, the partner infected with HIV was female.

All participants were aged 18 years or older, were sexually active, and were not using antiretroviral therapy. Additionally, all HIV-positive partners in the trial had herpes simplex virus type 2.

The researchers monitored rates of HIV-acquisition by HIV-negative women taking oral hormonal contraceptives or who received Depo-Provera shots. They also monitored rates of HIV-transmission from HIV-positive women taking hormonal contraceptives to their HIV-negative male partners.

All participants received HIV-prevention services, including counseling, free condoms, and treatment for sexually transmitted infections.

Results showed that HIV-negative women who used hormonal contraception, either in pill form or injected, were twice as likely to contract HIV from their HIV-positive male partners as women who reported using other forms of birth control or no birth control.

In addition, HIV-positive women who used hormonal contraception were twice as likely to transmit the virus to their uninfected partners as women who did not.

However, the study authors noted that not enough women in the study used birth control pills (rather than Depo-Provera) to draw definitive conclusions about the pill form of contraceptives.

The study authors also found that women using Depo-Provera had higher levels of HIV in the genital tract, even though the levels of HIV in their blood were the same. The researchers suggested that the higher level of HIV in the female genital tract might be a mechanism for increased risk of HIV transmission.

The researchers stated that a randomized trial is needed to definitively establish the risk of HIV associated with the contraceptives since the current study did not take into account factors such as contraception adherence and brand of contraception used.

For more information, please see the article in The Lancet Infectious Diseases (abstract) or the press release from the University of Washington.

Based on their results, the authors of the study suggested that genetic factors that may contribute to abnormal body fat redistribution and high cholesterol levels could eventually be used to guide HIV treatment decisions.

Drug-associated side effects are one of the major concerns associated with the use of antiretroviral therapy. Common long-term side effects of treatment include lipodystrophy, characterized by abnormal body fat redistribution, and metabolic syndrome, which includes insulin resistance, high cholesterol levels, high blood pressure, obesity, and type 2 diabetes.

According to the authors, studies of HIV-positive patients treated with antiretrovirals have shown that lipodystrophy can result in serious psychological problems and stigma, eventually leading to treatment non-adherence. Metabolic syndrome increases the risk of heart disease.

In this study, researchers from Italy examined the link between various genetic variations and the risk of lipodystrophy and high cholesterol in HIV-positive people starting antiretroviral therapy.

The study included 174 Caucasians who had started antiretroviral therapy. The majority (68 percent) of participants were male, and the median age was 38 years at treatment initiation.

Researchers analyzed participants’ DNA for seven possible genetic variations that they suspected, based on previous research, could be linked to a higher risk of lipodystrophy or metabolic syndrome. They also collected information on participants’ age, gender, weight, antiretroviral regimen, and viral load (amount of HIV in the blood).

Most of the participants (83 percent) received a protease inhibitor-based regimen as their initial regimen; the remainder were treated with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen.

During a median follow-up period of about four years, more than half of the participants developed some form of lipodystrophy. Almost 30 percent developed abdominal fat accumulation, and 36 percent developed lipoatrophy, which involves abnormal fat wasting on the face, limbs, and buttocks.

In addition, 29 percent of participants developed high overall levels of cholesterol. About 36 percent developed high “bad” cholesterol levels over the course of the study, and 19 percent of participants developed high levels of triglycerides. Two-thirds (66 percent) developed low levels of “good” cholesterol; low “good” cholesterol levels are linked to a higher risk of heart attack.

The researchers found that participants with a particular genetic variant, called MDR-1 3435 TT, were less likely to develop abdominal fat accumulation, with a risk one fifth of that of other participants. They also found a second variant, TNF 308 GG, that doubled the risk of abdominal fat accumulation. These variants were present in 26 percent and 78 percent of participants, respectively.

The researchers hypothesized that these variants could have effects on the way the body metabolizes antiretrovirals – reducing the amount of lipodystrophy-causing drugs in the blood, for example – or on the way it regulates fat accumulation and breakdown.

In addition, the researchers found several variants that affected cholesterol and triglyceride levels. The genetic variant TNF 238 GG was associated with a six-fold higher risk of low “good” cholesterol levels, while a second variant, LPL S477X, decreased the risk of high “bad” cholesterol levels by a little less than two thirds. These variants were present in 85 percent and 26 percent of participants, respectively.

For high triglyceride levels, the variant APOEe 3/3 decreased the risk by about three fourths, while the APM1 276 GT variant increased the risk by about three-fold. The variants were present in 65 percent and 34 percent of participants, respectively.

Aside from genetic variants, the researchers found that women were 2.5 times more likely to develop trunk fat accumulation but were less likely to have low “good” cholesterol levels compared to men. Use of an NNRTI rather than a protease inhibitor as a third drug in the initial antiretroviral regimen was also linked to a decreased risk of lower “good” cholesterol levels after starting treatment.

Higher viral loads were associated with about double the risk of developing low “good” cholesterol levels after starting antiretroviral therapy. Co-infection with hepatitis C virus and older age were associated with a higher risk of increased “bad” cholesterol levels.

The researchers stated that further studies that include different populations, such as non-Caucasians, and exposure to varying antiretroviral agents are necessary to confirm their results. They also suggested additional research into the actual mechanisms linking genetic variations with higher or lower risk of lipodystrophy and cholesterol levels.

For more information, please see the study in AIDS Research and Human Retroviruses.

The authors of the review recommended that in certain cases, patients should consider switching drug regimens or stopping antiretroviral therapy during chemotherapy.

The authors also emphasized the need for more clinical trial data about the combined use of antiretroviral therapy and anti-cancer drugs in patients with both cancer and HIV.

With the introduction of highly active antiretroviral therapy (HAART), AIDS-related complications and death have become less common; AIDS-defining cancers like Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer have decreased.

However, non-AIDS-defining cancers, including Hodgkin’s lymphoma and anal, lung, and testicular cancer, have become more common in HIV-positive people (see related AIDS Beacon news).

As a result, information about potential drug interactions and the combination of antiretroviral and cancer drugs in HIV-positive cancer patients is increasingly important. To date, little is known about the possible overlapping side effects of antiretrovirals and cancer drugs and the interactions of the two different types of drugs.

Antiretrovirals May Worsen Side Effects Of Certain Cancer Drugs

One major concern about combining antiretroviral therapy and chemotherapy is the potential for overlapping side effects. Several antiretrovirals have similar side effects as certain chemotherapy agents, and combining the two may increase the rate or severity of these effects.

Several of the side effect concerns deal with older antiretrovirals. Zidovudine (Retrovir), for example, has been associated with low white blood cell counts (neutropenia), which puts some patients at risk for infections. Many chemotherapy regimens are also associated with low white blood cell counts.

The review authors recommended that an alternative to zidovudine be used when possible during chemotherapy; if not, chemotherapy drugs that have less effect on white blood cells should be used and the patient’s white blood cell count should be carefully monitored.

Other anti-HIV drugs like didanosine (Videx) and stavudine (Zerit) are often associated with peripheral neuropathy, a nerve condition that causes pain, numbness, or tingling in the extremities. Since some classes of cancer drugs, specifically platinums (e.g., cisplatin, carboplatin), taxanes (such as paclitaxel (Taxol), Taxotere (docetaxel)), and vinca-alkaloids (e.g., vincristine (Oncovin), vinblastine (Velban)), may also cause peripheral neuropathy, the review authors recommended that physicians substitute a different chemotherapy drug with fewer overlapping side effects, substitute a different antiretroviral, or ask patients to temporarily discontinue antiretroviral therapy.

Some newer antiretrovirals may also cause problems when combined with chemotherapy drugs. The anti-HIV drugs Reyataz (atazanavir), Kaletra (lopinavir/ritonavir), and Invirase (saquinavir mesylate) are associated with longer QT intervals, a problem in which the heart takes an abnormally long time to recharge between beats.

Several anticancer drugs – including anthracyclines such as doxorubicin (Adriamycin) or daunorubicin (Cerubidine), arsenic trioxide (Trisenox), Sprycel (dasatinib), Tykerb (lapatinib), Tasigna (nilotinib), Sutent (sunitinib), and tamoxifen – are also linked with longer QT intervals. Because of the risk of sudden death associated with long QT intervals, the review authors recommended avoiding combinations of these drugs.

The authors noted that newer anticancer agents are more selective at killing cancer cells and may cause fewer side effects.

Interactions Between Anticancer Drugs And Antiretrovirals

Since antiretrovirals and chemotherapy drugs are often metabolized by the body in the same way, there is a high potential for drug-drug interactions. These may result in drug concentrations in the blood that are higher or lower than expected, leading to more side effects or reduced efficacy.

Since not many studies have been conducted on antiretroviral-chemotherapy drug interactions, scientists have tried to predict which drugs may interact based on what is known about how the drugs are metabolized.

In terms of antiretrovirals, the reviewers noted that Norvir (ritonavir)-boosted regimens may be of concern because Norvir is known to affect an enzyme that metabolizes many cancer drugs. Many physicians search for alternatives to Norvir-based regimens during chemotherapy.

Preliminary results from a study on Sutent presented this week at the American Society of Clinical Oncology meeting suggest that patients taking Norvir-based antiretroviral therapy may be more likely to experience side effects. The study, part of the AIDS Malignancy Consortium set of clinical trials, is one of the first to investigate drug-drug interactions for chemotherapy drugs and antiretrovirals.

For chemotherapy drugs, the reviewers suggested, based on drug interaction predictions, that anticancer drugs like camptothecins (e.g., Hycamtin (topotecan), irinotecan (Camptosar)), alkylating agents (such as melphalan (Alkeran), busulfan), corticosteroids (e.g., dexamethasone (Decadron), prednisone), epipodophyllotoxins (such as etoposide, Vumon (teniposide)), taxanes, tyrosine-kinase inhibitors (e.g., Gleevec (imatinib), Sutent), and vinca-alkaloids may be especially likely to be affected by HAART.

There is also some evidence from case studies that Targretin (bexarotene), cyclophosphamide (Cytoxan), Taxotere, irinotecan, and vinblastine might interact with antiretroviral drugs.

According to the review authors, there is currently no guidance for dose adjustments of antiretroviral or chemotherapy drugs, partly because patients with HIV were excluded from early cancer treatment trials. Although the exclusion of HIV patients from cancer treatment trials is no longer allowed, the study authors indicated that it may take several years before guidelines will be available.

The authors noted that maintenance of the chemotherapy dosing and schedule is thought to be most important in treating cancer, and therefore cancer treatment must sometimes take priority over HIV treatment, despite the risks associated with stopping HAART. However, they also stated that oncologists must recognize that continuous HAART is necessary to prevent resistant strains of HIV, opportunistic infections, and eventual death.

For more information, please see the article in The Lancet (abstract).

The researchers speculated that gender-based issues were not discussed during visits with the women’s health care providers because clinicians had a lack of experience, comfort, or knowledge of these issues or expected that patients’ concerns would be attended to by other physicians.

“Clinicians caring for HIV-infected women need to incorporate regular discussions about the reproductive plans of their patients. These plans change over time and clinicians need to modify their recommendations and treatment strategies accordingly,” said Dr. Kathleen Squires, a physician at Jefferson Medical College of Thomas Jefferson University in Philadelphia and lead author of the study.

“The study suggested that there is substantial room for improvement to reach this goal,” she added.

Based on their results, the study authors recommended that practitioners discuss issues such as family and pregnancy planning with HIV-positive patients. They also recommended that clinicians discuss other treatment-related psychological, social, and emotional aspects of HIV and offer routine screening for depression and other problems.

The proportion of women with HIV in the United States has increased over the past two decades. As of 2006, women comprised about one quarter of the HIV-positive population in the U.S.

According to the study authors, HIV-positive women face a unique set of health, social, and psychological problems. HIV and antiretroviral therapy may affect women differently than men. Also, rates of depression tend to be higher among HIV-positive women compared with HIV-positive men.

In addition, the use of highly active antiretroviral therapy during pregnancy, together with use of caesarean sections and avoidance of breast-feeding, have reduced rates of mother-to-child HIV transmission in the U.S. to less than 2 percent. As a result, more women with HIV may consider pregnancy and childbirth.

However, there is little information available on the effectiveness with which medical providers address potential pregnancy in women with HIV, and few studies have examined the gender-specific health needs of women with HIV.

In this study, researchers conducted a survey with 700 HIV-positive women to get feedback about communication barriers with their health care providers. Participants were recruited from 29 AIDS information, counseling, and treatment centers across the U.S.

Participants had a median age of 42.5 years and had been receiving antiretroviral therapy for an average of eight years. Two hundred of the women were Caucasian, 200 were Hispanic, and 300 were African-American.

Concerns About Gender, Racial Differences In HIV Progression And Treatment

More than half of the women (55 percent) had never discussed gender-based differences in treatment response with their practitioners, even though 46 percent of the women thought their disease affected them differently than men. Caucasian and African-American women were least likely to have discussed this issue with their HIV health care providers. Also, women with male health care providers were less likely than women with female health care providers to have discussed this topic (41 percent versus 51 percent, respectively).

However, 96 percent of women who did discuss gender-based differences in treatment response with their practitioners were satisfied with the answers they received.

More than half of the women (59 percent) felt that their culture, ethnicity, or language affected the care they received. Hispanic and African-American women were more likely to report this issue than Caucasian women. Also, women in the South were more likely to report this issue than women in the West or Northeast.

About one third of the women had seen three or more providers since starting HIV treatment, and 43 percent said they had changed providers because of communication issues.

Childbearing And Caregiver Issues

More than a third of the women (39 percent) had children. Of the women who had been pregnant prior to the survey or who were considering pregnancy, nearly half (48 percent) were never asked by their health care providers if they had or were thinking about having children. More than half (57 percent) had not talked about treatment options with their practitioners before becoming pregnant.

Of the women who were pregnant or had been pregnant at the time of the survey, 42 percent were either “not very aware” or “not at all aware” of the treatment options available to pregnant women with HIV.

Overall, 61 percent of women felt they could have children if given appropriate medical care but 59 percent felt society strongly discourages them from doing so.

Women with HIV who lived in the South were more likely to feel society discouraged them from having children than those living in the Northeast or Midwest. Those who received care from a nurse practitioner or physician assistant were also less likely to experience this attitude than those treated by infectious disease specialists or general practitioners.

Fifty-two percent of the women identified themselves as caregivers, and 43 percent said living with HIV has made it harder for them to look after their families. More women in the South compared with the Northeast felt this way (50 percent versus 37 percent, respectively).

The researchers speculated that concerns about stigma may encourage women with HIV, especially those who are caregivers, to keep their HIV status confidential as long as possible and hesitate to seek early care.

Social Support And Depression

Most women in the survey thought factors such as suppressing viral load (amount of HIV in the blood), achieving long-term success with medications, and being able to live normal lives were important aspects of their treatment.

Women who wanted extra support beyond what their practitioners could provide found it through support groups, therapists, family, and friends. Most Caucasian women identified therapists as sources of additional support, while Hispanic and African-American women mostly identified support groups.

Women in the Midwest and Northeast were more likely to get extra support from a support group or therapist, while women in the South were more likely to get support from family and friends.

Seventy-three percent of women said they had struggled “a great deal” or “somewhat” in managing their daily lives, while one third of the women experienced changes in sleep patterns, loss of energy, unexplained aches or pains, feelings of sadness or worry, and anxiety.

In addition, 27 percent had five or more feelings commonly associated with depression, although other studies have reported higher rates of depression among HIV-positive women.

A majority of the women (58 percent) said they were comfortable talking to their providers about their depression-related feelings, but women in the South were less likely to feel comfortable than women in the rest of the country.

For more information, please see the study in AIDS Patient Care and STDs.

Based on these results, the authors of the studies emphasized the need for integrated HIV care that addresses mental health problems, safe sex behavior, substance use, and treatment non-adherence in HIV-positive youth. They also suggested that HIV-negative youth exposed to HIV perinatally (i.e., during pregnancy, labor, delivery, or breastfeeding) receive the psychological and social services offered through HIV clinics, regardless of their HIV status.

Although children with HIV are living longer and reaching adolescence with the advent of highly active antiretroviral therapy (HAART), few studies have examined the behavioral health risks and challenges that become more important as these youth live longer.

According to the study authors, HIV-positive youth may be especially likely to engage in risky behaviors because their families tend to live in poorer, urban communities affected by racism and discrimination, substance use, and violence. They also tend to live with single mothers and experience multiple changes in caretakers.

Stigma And Risky Behaviors Predict Depression In Youth With HIV

One study found that over 50 percent of HIV-positive teen participants who engaged in risky behaviors suffered from depression. The study also found that teens who felt stigmatized due to their HIV, were older, and who engaged in more risky behaviors were more likely to be depressed.

The study authors suggested that reducing stigma and detecting and treating depression early could help prevent depression symptoms from getting worse. They also speculated that this could increase the likelihood of healthy behaviors, such as treatment adherence and safer sex practices.

HIV-positive youth who admitted to at least one risky behavior, including substance use, risky sexual behavior, and treatment non-adherence, were recruited for the study. A total of 186 youth participated.

Results showed that the most common problem was substance use, at almost 66 percent of participants. In addition, 44 percent had issues with medication adherence, and 54 percent reported risky sexual behaviors.

More than half, 52 percent, met the clinical criteria for depression.

Analysis showed that teens who acquired HIV sexually or through drug use, were older, exhibited more problem behaviors, and indicated more feelings of stigmatization were more likely to be depressed.

Youth Exposed To HIV Are At Risk For Behavioral And Mental Health Problems, Regardless Of HIV Status

A second study of perinatally exposed HIV-positive and HIV-negative youth found that almost half were at risk of at least one behavioral health problem, including mental health problems, early onset of sexual activity, and substance use. The most common risk was mental health problems, which were reported by 28 percent of youth.

The study included 349 HIV-positive and HIV-negative children and teenagers exposed to HIV during their mothers’ pregnancies. All youth were aged 10 to 16 years and were recruited from 15 sites across the United States.

Most study participants were from poorer, minority communities and were African American. About half were male. On average, HIV-positive youth were slightly older, more likely to be African American, more likely to come from families with higher incomes, and less likely to be living with their birth mothers.

Results showed that behavioral health problems were common. Twenty six percent of HIV-positive youths and 33 percent of HIV-negative youths reported mental health problems. In addition, 18 percent of HIV-positive youth and 14 percent of HIV-negative youth reported recent substance use, with alcohol and marijuana use most common.

About 16 percent of study participants were sexually active, with an average age of 13 years and 12 years for first sexual encounter for sexually active HIV-positive and HIV-negative youth, respectively. Sixty-five percent of sexually active HIV-positive youth and 50 percent of sexually active HIV-negative youth reported having unprotected sex.

Thirty-four percent of HIV-positive youth reported failure to adhere to antiretroviral therapy.

HIV-positive youth living with their birth mother were three times more likely to have two or more behavioral health risks than youth who lived with another type of relative or an unrelated caregiver. Older age was also associated with a higher risk of behavioral health problems.

The researchers noted that further studies are required to identify factors such as social support, caregiver mental health, and family involvement that might decrease the likelihood of behavioral health risks in youth exposed to HIV perinatally.

For more information, please see the studies in the Journal of Pediatric Health Care (abstract) and AIDS Patient Care and STDs.

However, the study authors noted that their study was limited in that most of the children involved had advanced HIV infection and were underweight.

Based on their results, the researchers recommended postponing surgeries in HIV-positive children until they are one year old or older whenever possible. They also stated that infections should be carefully controlled and that antibiotics should be used wisely to reduce post-operation infections, especially drug-resistant infections.

The study authors suggested further research on the effects of HAART on the rate of surgical complications in children with HIV.

Due to several factors, including treatment of life-threatening complications of the disease and the need for routine surgery, children with HIV are increasingly undergoing operations.

For children in general, the risk of developing complications after surgery is affected by factors such as general health, fitness, and the presence of an accompanying disease, as well as the type and duration of the surgery.

Young age, accompanying diseases, major or emergency surgery, and poor nutrition increase the risk of complications after surgery.

For children with HIV, information on the rate and risk of post-surgery complications is scarce, making it difficult to weigh the risks and benefits of surgery.

In a recent study carried out in South Africa, researchers monitored HIV-positive children who underwent surgical procedures to measure the rates, types, and risk factors for complications after surgery. The study included 82 children under 5 years of age who were undergoing general surgeries.

Most of the children (83 percent) had advanced HIV disease according to the World Health Organization clinical stages for HIV-positive infants and children, meaning they had unexplained weight loss, diarrhea, or fever, or had certain infections found only in children with suppressed immune systems. In addition, 88 percent had moderate or severe immune suppression.

Half were malnourished, as measured by their weight for their age; 73 percent received highly active antiretroviral therapy (HAART).

Around 45 percent of the children had emergency surgery, and 34 percent had major surgery. Major surgeries were defined as operations of the stomach or chest, cancer removal, operations longer than 90 minutes, or blood vessel reconstructions. The average hospital stay was 4 days.

Results showed that 42 percent of the children developed complications after surgery. Seven percent of the children died in the hospital, all from infections.

The most common complications (65 percent) were surgical site problems, including wound infection, wound breakdown, and early recurrence of the surgically-treated condition.

Most of the remaining complications (30 percent) involved general infections, including hospital-acquired pneumonia, sepsis (severe infection that has spread via the bloodstream), and sepsis from intravenous lines.

Analysis showed that age younger than 12 months was associated with an increased risk of complications, as was having major surgery. Severity of HIV infection, malnutrition, and type of surgery were not associated with the risk of complications.

For more information, please see the study in The Journal of Pediatric Surgery (abstract).

“If specialty care is less needed than it used to be for HIV-infected patients, it turns out that primary care is more needed. Owing to the advances in HIV treatment, our patients are no longer dying: they are aging!” wrote Dr. Katz, director of the Los Angeles Department of Health Services.

Dr. Katz argued in the editorial that HIV is now largely a chronic disease with relatively routine care that could be provided by primary care physicians, as is the case with diabetes.

Most people with HIV now begin treatment with Atripla (efavirenz/emtricitabine/tenofovir), a once-daily pill containing three antiretrovirals that has simplified HIV treatment. In addition, viral load testing – which measures the amount of HIV in the blood and allows physicians to measure how effective HV treatment is – has become fairly routine.

Dr. Katz argued that with the newer drugs and monitoring abilities, patients with effectively suppressed viruses are unlikely to develop the opportunistic diseases that made HIV treatment so difficult in the 1980s and 1990s.

“The most common reason for a patient’s condition not being fully suppressed while receiving one of the conventional regimens is non-adherence, a primary care problem if ever there was one,” wrote Dr. Katz.

“The small percentage of patients who do not obtain a good response to a conventional regimen despite being adherent will need referral for specialty care,” he added.

Instead, the primary challenges faced by people with HIV are increasingly caused by other conditions, such as heart disease, bone loss, and other problems – issues which, according to Dr. Katz, are best dealt with by a primary care physician.

Primary Care Physicians May Fill In Gaps Left By Dwindling Numbers Of HIV Specialists

The Institute of Medicine (IOM) report, published last month, also recommended shifting more HIV care to primary care doctors, stating that decreasing numbers of HIV specialists, along with a growing HIV-positive population, are placing strains on the current United States healthcare system.

In addition, people with HIV are increasingly moving from urban centers to more rural areas where HIV-care providers are especially scarce.

The authors recommended that primary care physicians receive better training in caring for people with HIV and that medical students receive greater exposure to outpatient HIV care throughout school and post-graduate training.

Kathryn Hafford, a registered nurse and director of the Division of Disease Prevention of Virginia’s Department of Health, said in correspondence with the AIDS Beacon that fewer medical students are choosing to specialize in HIV care.

“The health care system is strained and does not have enough qualified providers to increase HIV testing and ensure availability of medical care. Older HIV physicians are leaving the field faster than new physicians are entering,” said Hafford, who was not involved with the report. “Physicians are often not choosing infectious diseases because they can make substantially more money in other specialties,” she added.

She agreed with the IOM that more training for primary care physicians is needed. “Providing increased awareness of HIV in curricula, as well as encouraging students to pursue primary care and HIV specialization could make a significant difference in the availability and quality of care,” she said.

“Faculty need to make sure students consider HIV when working with patients with other health issues because less media publicity, improved treatment regimens, and focus on HIV in developing countries have resulted in some people thinking HIV is no longer a problem in the U.S.,” she added.

The IOM report noted that 45 percent of HIV-positive individuals aged 15 to 49 years are eligible for antiretroviral therapy under current treatment guidelines but are not receiving it.

In addition, the introduction of the Patient Protection and Affordable Care Act and the accompanying elimination of certain eligibility requirements for Medicaid are likely to bring more people with HIV into the Medicaid program, increasing demand for HIV care.

Challenges Remain In Shifting HIV Care To Primary Physicians

A number of challenges remain before HIV care can be shifted to primary care physicians, including the fact there is also a growing shortage of primary care doctors. Providing more training in HIV care for students who plan to become primary care physicians may not be enough.

“With the cost of medical school so high, many students prefer to enter a specialty that will provide a higher salary,” said Hafford.

The IOM report noted that medical students face a financial disincentive to go into HIV care, with one physician in the report commenting that HIV physicians are relatively poorly paid and most HIV clinics would not be sustainable without government funding.

The authors of the report suggest financial and other incentives, such as loan forgiveness or scholarships, to encourage entry into HIV care. The report also advocates that Ryan White clinics, which provide HIV care but also broad range of medical and nonmedical services, serve as models for future care systems.

Paul Cleary, chair of the IOM’s Committee on HIV Screening and Access to Care, stated in correspondence with the AIDS Beacon that significant changes would be necessary to implement the recommendations in the report.

“We are at a very exciting juncture because of the release of the National AIDS strategy, but for the strategy to have a substantial impact we will need to address a wide array of regulatory and policy issues and make a concerted attempt to address the capacity issues described in the IOM’s report,” said Cleary.

“The Office of National AIDS Policy will develop responses and policies based on the information in the IOM’s report,” he added.

For more information, please see the editorial in the Archives of Internal Medicine (subscription required) or the IOM Report, or a related AIDS Beacon article on the benefits and drawbacks of transferring HIV care to primary physicians.

The study found that most children with HIV maintain viral suppression and high CD4 (white blood) cell counts despite having had extensive treatment. Starting treatment earlier was more likely to result in better outcomes.

The researchers stated that their results support current U.S. treatment guidelines for initiating therapy at higher CD4 percentages in children.

Dr. Russell Van Dyke, co-author of the study and an infectious diseases expert at Tulane University, stated in a press release that while children with HIV “are still infected and not cured, it’s surprising how well they’re doing considering what they’ve been through.”

“They’re going to school and doing all of the things that kids should do. Hopefully they will be living 50 or 60 years or more, so what’s going to happen 40 years from now is the real concern,” said Dr. Van Dyke.

Dr. Van Dyke noted that as HIV becomes a more chronic, treatable disease, clinicians are starting to focus more on solving long-term complications, such as coronary artery disease and neurological and cognitive problems that might occur in children born with HIV.

“We’re not seeing the deaths we used to see due to infections, but we’re starting to worry about longer-term complications. Some of these complications may be related to the HIV itself, or some may be related to the medications these kids are on,” he said.

However, he stated that he expects many of the children in the study to have a normal or almost normal life span.

Today, fewer than 250 children are born with HIV each year in the United States. Most children with HIV were born before the advent of highly active antiretroviral therapy (HAART) in 1996. When taken during pregnancy and childbirth, HAART reduces the chances of a mother passing HIV to her child from 25 to 30 percent to less than 2 percent.

Since HAART is associated with better viral control, fewer HIV-related illnesses, improved survival, and an improved quality of life in most children, researchers hypothesized that children born with HIV more recently may have better outcomes than children born before 1996.

In their study, the researchers analyzed data from 451 children born with HIV in the U.S. between 1991 and 2002. The average age of study participants was 12 years. Most of the children (70 percent) were African American, and most of the rest (24 percent) were Hispanic. Slightly more than half (53 percent) were female.

The researchers divided the children into four groups depending on when they were born (1991 to 1993, 1994 to 1995, 1996 to 1997, and 1998 to 2002) to account for changes in the availability and use of antiretrovirals over time.

Researchers measured the children’s CD4 cell percentages (the fraction of their white blood cells that are CD4 cells, the cells targeted by HIV) and viral loads (amount of HIV in the blood) at the time they enrolled in the study. CD4 cell percentages, rather than CD4 counts, were used because these vary less by age in young children; normal CD4 cell percentages should be above 25 percent.

They also analyzed the children’s treatment and medical histories, including when they started treatment and how many different antiretroviral drugs they had taken. Most of the children (86 percent) were receiving a HAART regimen at the start of the study, with 70 percent taking a protease inhibitor-based regimen and 16 percent taking a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. The rest were not taking HAART.

Results showed that the average CD4 percentage for participants was 33 percent; the majority of children (78 percent) had normal CD4 percentages of at least 25 percent.

In addition, 68 percent of the children had achieved viral suppression, defined in this study as less than 400 copies of the virus per milliliter of blood.

Further analysis showed that children who began antiretroviral therapy at a younger age, had achieved viral suppression, and had a higher nadir CD4 percentage were more likely to have a higher CD4 percentage. The nadir CD4 percentage is defined as the lowest CD4 percentage measured after HIV infection.

Children who had fewer previous treatment regimens, received HAART, and had been born in 1996 or later were more likely to have achieved viral suppression at the start of the study. Boys were also slightly more likely than girls to have achieved viral suppression.

Children who were taking HAART at the start of the study had an 80 percent lower risk of having a detectable viral load than children not receiving HAART. There were no differences between protease inhibitor-based regimens versus NNRTI-based regimens.

Results also showed that most of the children were highly treatment experienced. Study participants had taken a median of seven different antiretrovirals and five different treatment regimens, with a median of 11.4 years of antiretroviral treatment total.

For every additional regimen taken prior to enrolling in the study, the researchers found a 10 percent increase in the risk of a child having a detectable viral load at the start of the study.

The outcomes of the children varied depending on when they were born. Children born more recently began treatment at an earlier age, were more likely to have received HAART as their initial regimen, and had received fewer total treatment regimens.

They also had maintained higher average CD4 percentages throughout their lifetimes than participants born earlier and were less likely to have been diagnosed with AIDS.

The researchers stated that further studies are needed to investigate the modest association between gender and viral response in children. A study is also underway to assess the effects of viral resistance on treatment failure in children.

For more information, please see the study in the Journal of Acquired Immune Deficiency Syndromes (abstract) or the press release from Tulane University.

The researchers noted that all study participants were self-identified men who have sex with men, and the findings may not be applicable to HIV-positive men who have sex with women only.

Based on their results, the researchers recommended that HIV-positive men who are at risk for urinary tract problems be screened and treated accordingly.

Urinary problems are common in aging men. Possible risk factors for lower urinary tract problems in HIV-positive men include chronic urinary tract infections, use of highly active antiretroviral therapy (HAART), opportunistic infections, and direct effects of HIV on the nervous system.

Although evidence suggests HIV is linked with lower urinary tract symptoms and bladder function problems, previous studies have been small and took place before the advent of HAART.

In this study, researchers attempted to determine whether HIV is associated with increased risk of self-reported urinary tract problems in men. The study included 1,830 men who have sex with men. Of these, 323 (17.6 percent) were HIV positive. All participants were 30 years of age or older.

Participants filled in an Internet-based survey on lower urinary tract symptoms, such as intermittent urination, having a weak stream, straining, and incomplete emptying, known as voiding symptoms; as well as frequency, urgency, and the need to get up in the night to urinate, referred to as storage symptoms.

Results showed that more HIV-positive men had moderate or severe lower urinary tract symptoms (33.2 percent and 11.4 percent, respectively) compared to HIV-negative men (29.2 percent and 4.2 percent, respectively).

Further analysis showed that men with HIV were twice as likely to report severe urinary tract symptoms as men without HIV, even after accounting for other risk factors. HIV-positive men with a history of AIDS-defining illness or CD4 (white blood cell) counts less than 200 cells per microliter were 2.5 times more likely to report severe urinary tract symptoms.

Men with a history of AIDS-defining illness or low CD4 counts also had an increased risk of moderate and severe lower urinary tract symptoms than HIV-positive men with no history of AIDS-related illnesses.

HIV-positive participants were more likely to have coronary artery disease, high cholesterol or triglyceride levels, high blood pressure, and history of chlamydia, gonorrhea, urinary tract infections, and depression compared to HIV-negative men.

Risk factors for moderate urinary tract symptoms included older age, depression, diabetes, and history of urinary tract infections, prostatitis (inflammation of the prostate gland), or gonorrhea. Risk factors for severe symptoms included older age, depression, and high cholesterol or triglyceride levels.

The researchers suggested that future studies investigate the relationship between HAART and lower urinary tract symptoms in men with HIV.

For more information, please see the study in the Journal of Urology (abstract).

However, the results did suggest that treatment intensification may be more dangerous for patients with extremely low CD4 counts. The authors also noted that other studies have found that treatment interruptions lead to poorer prognoses and that current guidelines recommend against interrupting treatment.

Drug resistance is one of the main causes of antiretroviral drug failure. Individuals are considered resistant to an anti-HIV drug if their viral load (amount of HIV in the blood) does not remain low after treatment and/or testing confirms the presence of an HIV strain that is resistant to one or more classes of antiretroviral drugs.

Multi-drug resistant HIV, in which a person’s HIV is resistant to multiple classes of antiretrovirals, is associated with more limited treatment options, increased risk of AIDS-associated diseases, and death. Multi-drug resistance can arise from non-adherence to antiretroviral regimens, antiretroviral regimens that are only partially effective, or, for older HIV-positive adults, exposure to antiretrovirals sequentially rather than in combination prior to the advent of highly-active antiretroviral therapy.

Physicians primarily address drug resistance by changing a patient’s antiretroviral regimen to include anti-HIV drugs from different classes, particularly newer drug classes like integrase inhibitors. However, clinicians have also experimented with alternative strategies such as treatment intensification, in which a person is prescribed a regimen containing up to nine different antiretrovirals.

Alternative strategies may be particularly appropriate for people who cannot use newer antiretrovirals due to extensive drug resistance, treatment failure with newer drug classes, intolerable side effects, or limited access to newer, more expensive anti-HIV drugs. However, the safety and efficacy of these strategies have not been clearly established.

In this study, researchers compared the safety and efficacy of two different types of treatment interventions in people with multi-drug resistant HIV: switching to a “standard” antiretroviral regimen with up to four antiretrovirals versus switching to an intensified regimen with at least five anti-HIV drugs; and starting the new regimen right away versus interrupting treatment for 12 weeks before starting retreatment.

The study included 368 HIV-positive adults, 98 percent of whom were men. All study participants had CD4 (white blood cell) counts of 300 cells per microliter of blood or less and had either experienced treatment failure with two different antiretroviral regimens or had shown resistance to at least three classes of antiretrovirals (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors).

Participants were randomly assigned to either a new standard regimen or a new intensified regimen. Additionally, half were selected to start treatment immediately, while the other half waited 12 weeks to begin treatment.

The researchers monitored CD4 counts, viral loads (amount of virus in the blood), and the time to the first AIDS-related illness or death for each participant. Participants were followed for a median of four years.

Results showed that after 24 weeks, there were no significant differences in CD4 counts or viral loads between the groups. Over the course of the study period, CD4 counts increased by an average of about 100 cells per microliter and average viral loads decreased to around 1 percent of their original values for participants in all treatment groups.

Results also showed that 35 percent of participants died during the study period. The researchers determined that 52 percent of the deaths were HIV-related, 2 percent were due to antiretroviral medications, and the rest were either non-HIV-related or of undetermined causes.

In addition, 27 percent of participants experienced an AIDS-related illness during the study period, the most common of which were esophageal thrush (a yeast infection in the esophagus) and pneumonia.

There were no significant differences in time to death or AIDS-defining illness among the treatment groups. There was also no significant difference in the number or type of AIDS-defining illnesses between treatment groups.

However, for participants with baseline CD4 counts lower than 36 cells per microliter, more deaths occurred with intensification of treatment compared with standard treatment (71 percent versus 49 percent).

For more information, please see the study in PLoS One.

The researchers speculated that injection drug users might experience faster disease progression than non-injection drug users due to longer drug history, poorer general health status, or larger drug dose intake via injection, which may lead to poorer antiretroviral drug adherence.

The researchers also noted that since they looked at non-injection drug use in general, rather than at particular types of illegal drugs such as cocaine or methamphetamines, it is still possible that certain non-injection drugs are associated with faster disease progression.

Based on their results, the researchers suggested that clinicians consider drug and alcohol abuse screening for patients with HIV during regular clinic visits and direct them to drug treatment programs if appropriate.

They also stated that drug screening and treatment programs should be offered to both injection drug users and non-injection drug users, although injection drug users especially require attention.

In general, HIV-positive people with a history of drug use tend to start highly active antiretroviral therapy (HAART) later, have poorer adherence to HAART, and have poorer control of the HIV virus.

Injection drug use is associated with faster HIV disease progression even among people receiving HAART. However, little is known about the relationship between non-injection drug use and HIV disease progression.

The few studies conducted so far with non-injection drug users have yielded mixed results. Several studies have indicated that crack cocaine may be linked to faster disease progression (see related AIDS Beacon news); however, another study found no relationship between marijuana and other recreational drugs and HIV progression.

This study involved 1,712 HIV-positive participants, each of whom was either an injection drug user, a non-injection drug user, or had no history of drug use. The median follow-up period was 2 years.

More than half the participants were Caucasian and almost a quarter were women. A third of the participants had received HAART prior to beginning the study and 40 percent began HAART during the study.

Results showed that 10.5 percent of study participants experienced an AIDS-related illness during the study period and 10.7 percent of participants died. The overall probability of AIDS-free survival after one year was 85 percent for injection drug users, 92 percent for non-injection drug users, and 91 percent for nonusers.

Further analysis showed that injection drug users had a nearly two-fold higher risk of progressing to AIDS or dying than nonusers. The risk of progression or death for non-injection drug users was not statistically different from the risk in nonusers.

The researchers emphasized that the study was limited in that it did not include cause of death information. Some deaths may not have been related to AIDS, since both injection and non-injection drug use is associated with increased risk of death.

Also, the study did not consider HAART adherence, which could be a factor in the relationship between drug use and HIV disease progression.

The authors recommended additional studies that consider type and frequency of drug use, as well as studies with longer follow-up periods.

For more information, please see the study in the Journal of Substance Abuse Treatment (abstract).

The results may explain why age-specific cervical cancer rates among HIV-positive women have not increased with the rise of highly active antiretroviral therapy (HAART) even though women with HIV are living longer. However, the researchers stated that they still expect the overall rates of cervical cancer in the HIV-positive population to increase since older women have higher rates of cervical cancer.

The authors also suggested that conflicting findings in previous studies of HAART, human papillomavirus (HPV), and cervical lesions may be due to differences in patient adherence or effectiveness of HAART regimens.

HPV is one of the most common sexually transmitted diseases. Around 75 percent to 80 percent of women with HIV also have HPV. Women with HIV have a weakened immune system, which allows HPV to survive in the cervix and cause pre-cancerous lesions. As a result, cervical cancer caused by HPV is especially common in HIV-positive women.

Studies on the effects of HAART on HPV and cervical cancer have shown mixed results. Since HAART allows women with HIV to live longer, it raises the likelihood of exposure to HPV and also allows for longer HPV persistence and the accumulation of mutations that lead to cervical cancer. Moreover, as HIV-positive women live longer, they enter the age groups in which cervical cancer rates are greatest.

HAART can, however, restore the functioning of the immune system. An effective immune system is strongly linked with prevention of new strains of HPV, shorter HPV infections, and less pre-cervical cancer in women with HIV.

In this study, researchers investigated whether rates of HPV infection and pre-cervical cancer are related to patient adherence to their HAART regimen and the efficacy of HAART in suppressing HIV.

The study included 286 HIV-positive women starting HAART for the first time. The researchers measured rates of HPV infection and pre-cervical cancer before and after HAART initiation. They also measured the adherence of the study participants to their antiretroviral regimens and their viral loads (amount of HIV in the blood).

Adherent women were defined as those who took their medications as prescribed at least 95 percent of the time; the rest were considered non-adherent. HAART was considered effective if a woman’s viral load was reduced by more than 90 percent or to undetectable levels.

Results showed that after starting HAART, the number of women who tested positive for HPV strains known to cause cervical cancer decreased by 36 percent among adherent women, compared to 12 percent among non-adherent women.

In addition, the number of women who tested positive for cancer-causing HPV decreased 20 percent in patients on effective HAART, but increased slightly for those on ineffective HAART.

Women adherent to HAART were less likely to contract new cancer-causing HPV strains. The rate of detection of new HPV strains decreased 33 percent for adherent women versus 9 percent in non-adherent women.

Results revealed that adherent and non-adherent women had a similar decrease in the rate of development of pre-cancerous cervical lesions. However, women adherent to HAART had higher clearance rates for lesions than women who were non-adherent.

Similarly, the effectiveness of HAART did not affect the number of pre-cancerous lesions developed, but effective HAART was associated with greater lesion clearance rates compared to before the women started treatment while ineffective HAART was not.

The researchers acknowledged several limitations of the study, including the fact that it is not possible to be completely certain how the data relate to actual cervical cancer rates since the study only considered the development of HPV and pre-cervical cancer. The researchers recommended longer-term follow up studies to examine rates of cervical cancer.

For more information, please see the study in The Journal of Infectious Diseases.

“Phylogenetic analysis is more powerful in its ability to exclude certain scenarios,” said Professor Anne-Meike Vandamme of the Rega Institute for Medical Research at Katholieke Universiteit Leuven and coauthor of the Lancet article, in correspondence with The AIDS Beacon. “Phylogenetics can prove that people cannot have infected each other, but it can never prove that people infected each other.”

The experts listed several guidelines for scientific experts to follow in order to prevent the misuse of HIV fingerprinting evidence in HIV criminal transmission trials. The recommendations include using a sufficient number of comparison samples from other people in the area who have HIV; not informing experts as to which HIV samples are from the accused and which are from the accuser while the tests are being run; and taking special care to correctly word their findings in light of the limitations of the technique.

HIV Criminal Transmission And Phylogenetic Analysis

Criminal transmission of HIV is defined as the intentional or reckless infection of another person with HIV. In most states, it is illegal for a person with HIV to have unprotected sex without disclosing his or her HIV status.

HIV phylogenetic analysis is a technique that examines small differences in HIV virus genes in order to determine how closely related two samples of HIV are. In cases of criminal transmission of HIV, it has been used to compare samples taken from the alleged victim and from the accused individual in an attempt to determine whether the accused was the source of the transmitted HIV.

Phylogenetic analysis has been used as part of the overall evidence in several HIV criminal transmission trials in the United States, including a 2004 case in Washington and a 2009 case in Texas. In both cases the accused individuals were convicted.

Last year a scientific article (abstract) published in the Proceedings of the National Academy of Sciences (PNAS) described how HIV phylogenetic analysis was used to identify the source of HIV in these two criminal cases.

Limitations Of HIV Phylogenetic Analysis

The new Lancet article was written partly as a response to the PNAS study. Several experts in phylogenetic analysis cautioned that the technique has the potential to be misused and that by itself, it cannot prove transmission of HIV.

Unlike human DNA samples or fingerprints, HIV is not unique to an individual. If scientists find a person’s DNA or fingerprints at a crime scene, for example, they can be fairly certain the person was at the scene.

HIV, on the other hand, is not unique; several people can have very similar HIV, particularly if they were infected by the same person. In addition, even within one person, HIV mutates so rapidly that HIV samples taken at different points in time will look different. This means that no two HIV samples (even within one person) will ever be identical, which makes it difficult to determine the source of a transmitted virus.

Other factors may complicate the matter further, such as the possibility of unknown third parties who may be involved in the transmission of HIV.

“A lot of infected people don’t know that they are infected; the source of a particular infection can be someone who is not diagnosed or someone who is diagnosed but not among the people sampled, which is a big problem,” said Prof. Vandamme.

“There can be a male who gives the virus to another male, who gives it to another,” she explained as an example. “There is one person in between. If you don’t have the virus from the male in between [for comparison], it will lead to the same conclusion as if that first male had immediately infected the third male.”

As a result, the authors argue there can never be complete confidence that the accused individual infected the other person based on phylogenetic analysis alone.

Another problem, says Prof. Vandamme, is that scientists may be giving a false impression of what phylogenetic analysis is capable of. Prof. Vandamme said she has been in several court cases where the scientific experts from the prosecution failed to carefully communicate what could and could not be concluded from the technique.

“The issue here is the concept of ‘fingerprinting’ as identifying someone as a person who matches the person the court is looking for. But ‘fingerprinting’ really gives the feeling of identifying a perfect match, which you can never do with HIV,” said Prof. Vandamme.

Instead, expert witnesses need to make sure they also include a discussion of the technique’s weaknesses. “If you don’t choose the right wording to express what you can and cannot say you risk giving false confidence. You have to say what you can say, but also stress what you cannot say and that’s not always done properly,” she added.

Debate Within The Phylogenetic Analysis Community

Professor David Hillis, coauthor of the PNAS article published late last year, agreed with the guidelines proposed by the authors of the Lancet article and stressed that he followed similar rules in his own study. He also stated that in the Washington and Texas cases, there was additional evidence and phylogenetic analysis was not used by itself for conviction.

He also agreed that, “Analyses should not be termed ‘HIV fingerprinting.’ Rather, the correct term is ‘HIV phylogenetic analysis.’”

However, Prof. Hillis does believe that in certain cases, phylogenetic analysis can be used to determine whether one person transmitted the virus to another. “A more detailed analysis of multiple strains from the victim and the suspect, as we conducted in our recently published paper, can indeed support or reject a hypothesis about the direction of transmission between suspected transmission pairs,” said Prof. Hillis.

Prof. Hillis’ analysis relied on the fact that HIV transmission is commonly caused by only a single virus particle, which then mutates and evolves into several different strains. By looking at these multiple strains and how they are related to the HIV in the person suspected of transmitting the virus, Prof. Hillis argues that phylogenetic analysis can infer the directionality of the transmission.

Nonetheless, Prof. Vandamme and many other phylogenetic experts remain unconvinced. “No phylogenetic inference, no matter how confidently done, allows the exclusion of alternative scenarios with an intermediate transmission from one or more unsampled individuals,” she argued. “This method, like any other phylogenetic method in HIV forensics, does not exclude an indirect, rather than direct, link.”

“As forensic experts, we see phylogenetic analysis increasingly being relied on in convictions by criminal courts and with this [PNAS] paper, we fear a renewed false confidence about the reliability of phylogenetic analysis to correctly reconstruct an HIV transmission history, which may lead to risks of miscarriages of justice,” added Prof. Vandamme.

For more information, please see the article in the Lancet Infectious Diseases (subscription required).

“Our study is important as it has demonstrated that many drugs which are effective in other neuropathic pain states (and frequently used to treat painful HIV-SN [HIV-associated sensory neuropathy]) have no evidence of efficacy in painful HIV-SN,” said Dr. Tudor Phillips, lead author on the study, in correspondence with The AIDS Beacon.

Dr. Phillips also pointed out that, while the trials in included in the review found that high-dose topical capsaicin is effective, there is also a new trial underway that indicates it may be no more effective than a placebo. He also stated that the nerve growth protein will not be developed further because the required injections are too painful.

“This leaves very few evidence-based treatments available for clinicians to use. Consequently there is a real need to develop new treatment strategies for painful HIV-SN,” he added.

The authors suggested that one promising treatment for this condition may be the drug Cymbalta (duloxetine). Cymbalta is an antidepressant that is also used to treat diabetic neuropathy, a condition similar to HIV-SN. They also recommended that further studies be conducted with pain relievers in the opioid class, which includes drugs such as morphine, oxycodone (OxyContin), and hydrocodone.

HIV-associated sensory neuropathy (HIV-SN) is a nerve condition that causes pain, numbness, or tingling in the extremities. It can be caused both by the virus itself and by some HIV treatments, particularly the nucleoside reverse transcriptase inhibitors didanosine (Videx) and stavudine (Zerit).

The condition affects about 40 percent of all HIV patients on antiretroviral therapy and may become more common as more HIV-positive individuals begin antiretroviral treatment.

Currently, there are a variety of treatments prescribed to treat HIV-SN, but information on their efficacy for HIV-SN is limited because many of the drugs were designed to treat other conditions. For example, Lyrica (pregabalin) is approved to treat seizures, and amitriptyline is an antidepressant.

In their review, researchers sought to evaluate the effectiveness of these two drugs, as well as other commonly-used pain relievers, in treating HIV-SN. The review was based on 14 randomized, controlled clinical trials that investigated HIV-SN treatments.

Results showed that the only treatments to demonstrate greater efficacy than a placebo were smoked marijuana, high-dose topical capsaicin, and nerve growth factor. Topical capsaicin is a medicated cream or lotion for relieving joint and muscle pain that contains the active ingredient from chili peppers. Nerve growth factor is a small protein important for the growth, maintenance, and survival of certain nerve cells.

In contrast, the pain relievers amitriptyline, gabapentin (Neurontin) (a drug originally developed for the treatment of epilepsy that is now widely used as a pain reliever), Lyrica, prosaptide, peptide T, acetyl-L-carnitine, mexilitine (Mexitil), and low-dose topical capsaicin were no more effective in treating HIV-SN than placebos.

Lamotrigrine (Lamictal), another drug that was examined, may have been effective specifically in patients whose HIV-SN was linked to taking certain antiretrovirals known to cause the condition. For patients with HIV-SN in general, however, it was not more effective than a placebo.

Of the three drugs that demonstrated efficacy, only high-dose capsaicin is currently approved by the United States Food and Drug Administration (FDA). The FDA does not recommend smoked marijuana as therapy and nerve growth factor is not approved by the FDA.

The researchers did note that their results are somewhat limited by the lack of high-quality randomized, controlled trials investigating HIV-SN pain treatment. They added that their analysis was complicated by differing study designs and sizes.

The authors also pointed out that some of the trials included in the review did not take into account additional pain relievers being used by participants during the trials or whether participants had previously failed other pain relieving therapies. These conditions might have affected the results of the trials.

For more information, please see the study in PLoS One.

The study authors argue that if these markers are validated by further study, they could be used to help guide decisions concerning the timing of antiretroviral therapy in patients with AIDS and recent cryptococcal meningitis.

“These biomarkers might be an objective tool to stratify the risk of CM-IRIS [cryptococcal meningitis-associated immune reconstitution inflammatory syndrome] and death, and could be used clinically to guide when to start antiretroviral therapy,” said the authors in a press release.

Cryptococcal meningitis is an infection in the brain that is caused by a fungus. It is a common opportunistic infection (an infection that occurs in people with compromised immune systems) in people with AIDS.

Treatment with antiretroviral therapy suppresses HIV and helps restore the immune system, allowing the body to fight off such opportunistic infections. However, antiretroviral therapy can also trigger a condition called immune reconstitution inflammatory syndrome (IRIS) in people with AIDS who also have a bacterial or fungal infection.

IRIS occurs when the recovering immune system overreacts to these other infections with uncontrolled inflammation, characterized by swelling and redness that leads to widespread tissue damage. It is fatal for up to one third of all people with the condition.

For people who have had cryptococcal meningitis, CM-IRIS (cryptococcal meningitis-associated IRIS) may be caused by the immune system overreacting to remaining cryptococcal meningitis fungus particles and proteins in the body.

Currently, there is no way to predict which patients will develop CM-IRIS when they start antiretroviral therapy.

In this study, researchers tried to identify markers that might be used to predict and diagnose CM-IRIS. In particular, they looked at the levels of remaining fungal proteins in the blood as well as levels of certain immune system proteins that indicate inflammation.

The researchers followed 101 antiretroviral therapy-naïve Ugandans for one year after beginning antiretroviral treatment. All the study participants had AIDS at the start of the study and had also recently had cryptococcal meningitis.

Over the course of the study, 45 percent of study participants developed IRIS; deaths occurred in 36 percent of these patients. In contrast, deaths occurred in 21 percent of study participants who did not develop IRIS.

The researchers found no connection between risk of developing IRIS and various parameters such as CD4 (white blood cell) counts, starting viral loads (amount of HIV in the blood), the success of antiretroviral therapy at suppressing the virus, or how soon participants started antiretroviral therapy after receiving treatment for their cryptococcal meningitis infection.

However, results did reveal that prior to starting antiretroviral therapy, patients who developed CM-IRIS had four-fold higher levels of cryptococcal meningitis antigens, inflammatory molecules produced by the fungus, than patients who did not develop CM-IRIS. The researchers suggested that the immune systems of people who developed CM-IRIS may not have been as effective at clearing out the fungus.

Researchers also found that prior to antiretroviral therapy, study participants who developed IRIS had higher levels of two kinds of inflammatory proteins, called interleukin-4 and interleukin-17, as well as decreased levels of four other immune system proteins.

Using these results, the researchers were able to develop a mathematical formula involving the levels of these seven markers – the fungus antigens plus the six immune system proteins – to determine whether patients were at high, moderate, or low risk of developing CM-IRIS.

They were also able to show that the levels of certain immune proteins could predict the risk of death from CM-IRIS after starting antiretroviral therapy.

According the to researchers, doctors could potentially measure the levels of these markers in the blood of a patient with AIDS and cryptococcal meningitis and then use the formula to determine whether starting antiretroviral therapy could put them at risk for CM-IRIS.

They also hope that knowing which immune proteins are involved in IRIS will help scientists determine how best to treat CM-IRIS in the future.

However, the researchers stated that the markers identified in the study as indicators of CM-IRIS need to be confirmed in larger studies involving patients from more countries before they can be used by clinicians to predict the risk of CM-IRIS and death.

For more information on the study, please see the article in PLoS Medicine.

Researchers Report Promising Phase 1/2 Results For New HIV Drug VIR-576 – Results of a small Phase 1/2 clinical trial for VIR-576, a new type of antiretroviral drug under development by the small German company VIRO Pharmaceuticals, showed that it successfully reduced viral loads (amount of HIV in the blood) in treatment-naïve patients. No serious side effects were reported. VIR-576 is a new entry inhibitor, a relatively new class of antiretrovirals that includes Selzentry (maraviroc) and Fuzeon (enfuvirtide). VIR-576 works by binding to a protein on the surface of HIV, preventing it from attaching to and infecting cells. It works somewhat differently than either Selzentry or Fuzeon, and its developers hope that HIV will be less able to form drug resistance to VIR-576 than to most other antiretrovirals. While VIR-576 itself has some drawbacks – large doses are necessary and they must be administered intravenously – the researchers concluded that drugs of this type are promising and should be developed further. For more information, please see the article in Science Translational Medicine (abstract).

AIDS Healthcare Foundation Sues Tibotec Therapeutics For Overcharging – The AIDS Healthcare Foundation (AHF), a California-based HIV/AIDS treatment and advocacy group, has filed a lawsuit against Tibotec Therapeutics for overcharging for antiretroviral drugs purchased under a government pricing program. The program requires drug manufacturers to provide drugs to specific groups at reduced costs. Groups eligible for reduced prices are largely nonprofit and governmental medical providers, including AHF. AHF claims that pharmaceutical companies in the pricing program were required to lower prices beginning January 2010, but that Tibotec only implemented the changes in July 2010. AHF has also filed suit against Bristol-Myers Squibb on a similar basis. For more information, please see the AHF press release.

Clinical Trial To Investigate The Effects Of Egrifta On HIV-Associated Fat Accumulation Is Currently Recruiting Participants – A Massachusetts study is investigating the effects of Egrifta (tesamorelin) on lipodystrophy (abnormal fat accumulation) in the muscle and liver, insulin sensitivity, sugar metabolism, cardiovascular health, and inflammation in people with HIV. These conditions are often associated with HIV and HIV treatment. The researchers believe Egrifta will reduce fat accumulation in the liver and muscle, decrease inflammation and possibly improve sugar metabolism. The study is currently recruiting participants in the Boston area who are aged 18 to 60 years and have lipodystrophy. For more information, please see the United States Clinical Trials Registry.

The researchers concluded that transmitted drug resistance is still a problem and emphasized the need for early diagnosis and aggressive treatment strategies for people with drug-resistant HIV.

HIV that is resistant to treatment with antiretrovirals is one of the most common reasons that treatments fail. When people with drug-resistant HIV pass their virus on to others, those newly infected people have fewer treatment options.

Drug-resistant HIV is usually transmitted by people who are undergoing antiretroviral therapy but fail to achieve viral suppression (an undetectable amount of HIV in the bloodstream), or by people who acquire drug-resistant HIV and transmit it before beginning antiretroviral therapy.

As more and more HIV-positive people take antiretroviral drugs for longer lengths of time, the prevalence of drug-resistant HIV has increasingly become a cause for concern. In many areas, 10 percent to 20 percent of new HIV infections involve transmission of drug-resistant HIV.

Beginning in late 2007, new HIV medications including Isentress (raltegravir), Selzentry (maraviroc), and Intelence (etravirine) were introduced.

Researchers predicted that these newer antiretrovirals would better suppress transmission of drug-resistant forms of HIV if the main driver was transmission by people on antiretroviral therapy, since the new drugs would be better at suppressing HIV that is resistant to older medications.

Conversely, researchers hypothesized that if the main driver of transmitted drug resistance was treatment-naïve people with drug-resistant HIV, the impact of improved antiretroviral therapy would be minimal or delayed until the new drugs become widely available.

In this study, the researchers tried to determine whether the new antiretrovirals had an effect on transmission rates for drug-resistant HIV in the years since they were approved. To do so, they used results from a study that was designed to measure rates of transmitted drug resistance between 2002 and 2009.

The study included 372 people in San Francisco who had tested positive for HIV within 12 months of enrollment. Most of the participants (96 percent) were men who have sex with men; 9 percent of participants were injection drug users.

Participants were divided into two groups: those who tested positive for HIV between 2005 and 2007 and those who tested positive between 2008 and 2009. This allowed researchers to compare the prevalence of transmitted drug resistance before and after the introduction of new antiretrovirals in late 2007.

The researchers analyzed participants’ CD4 cell counts, viral load, and the presence of any drug resistance mutations displayed by their HIV.

Results showed that the prevalence of transmitted drug resistance more than tripled between 2003 and 2007 from 7 percent in 2003 to 24 percent in 2007. Between 2008 and 2009, the rate dropped to 15 percent of participants.

However, the researchers concluded that the difference was not statistically significant, and that overall, the chances of acquiring drug-resistant HIV in 2008 to 2009 were not significantly lower than the chances of acquiring drug-resistant HIV in 2005 to 2007.

The researchers listed two possible explanations for the study results: (1) poor antiretroviral therapy adherence and/or poor medical care in people who are on antiretroviral therapy or (2) considerable transmission of drug resistance via treatment-naïve individuals. Since other studies have indicated that more HIV-positive people in San Francisco have successfully achieved viral suppression in recent years, the researchers thought the second explanation was more likely.

The study authors stressed that there is a scarcity of data on the use of new antiretroviral medications in San Francisco and warned that delayed uptake of the new drugs will have a delayed impact on transmission of drug-resistant HIV.

As a result, they suggested that longer studies with participants from broader geographic areas are needed to allow for better comparisons of transmitted drug resistance rates before and after the introduction of novel anti-HIV drugs.

For more information, please see the study in PLoS One.

The authors suggested that combining Avandia (rosiglitazone) with a drug that blocks fat breakdown could help treat HIV-related pre-diabetes and lipoatrophy more effectively.

Avandia is a drug used to treat type 2 diabetes. It works by increasing the insulin sensitivity of fat cells, causing them to take in more glucose from the bloodstream.

HIV treatment, particularly with nucleoside reverse transcriptase inhibitors and protease inhibitors, is known to be associated with development of pre-diabetes, including insulin resistance (see related AIDS Beacon news). Researchers have speculated that Avandia could help improve pre-diabetes and related side effects in people with HIV.

Some studies have also found that Avandia could help relieve symptoms of lipoatrophy, another side effect of antiretrovirals in which fat is lost from the face, buttocks, and limbs. However, results have been inconsistent, with other studies showing no improvements in lipoatrophy.

In addition, Avandia has been shown to decrease the levels of triglycerides, a type of fat, in the bloodstream of people with diabetes. However, studies in people with HIV have not been as promising. Although Avandia was shown to improve insulin sensitivity, studies also showed that the drug actually increased levels of triglycerides and “bad” cholesterol.

The purpose of this study was to assess whether Avandia could help with insulin resistance and lipoatrophy in people with HIV. The researchers also attempted to understand the reasons for the mixed outcomes of treatment with the drug.

The study included nine HIV-positive men with lipoatrophy.  All participants were on stable HAART regimens for the duration of the study and had been for at least 6 months prior to enrolling in the trial. None of the men had diabetes, and any cholesterol-lowering drugs were stopped at least six weeks prior to the beginning of the study.

The participants were treated with Avandia daily for 3 months. The researchers measured participants’ blood insulin and glucose levels, triglyceride and cholesterol levels, body weight, and waist-to-hip ratio. In addition, the researchers measured the rates at which participants’ bodies broke down and built up fat.

Results showed that, consistent with previous studies, Avandia successfully reduced participants’ blood insulin levels and insulin resistance. However, also consistent with previous studies, Avandia did not reduce participants’ triglyceride or cholesterol levels.

The researchers did find that participants’ waist-to-hip ratios decreased due to an increase in hip circumference. The researchers suggested this might indicate that Avandia was helping participants gain or retain fat in regions affected by lipoatrophy, but the effects were mild and this hypothesis could not be confirmed.

Further investigation showed that Avandia significantly increased the rates of both fat breakdown and fat buildup within fat cells. Since both rates were increased, this had little effect on overall fat distribution or concentration of triglycerides in the blood.

The researchers noted that the drug’s effects on both rates may account for some of the mixed results observed in previous studies.

They concluded that because of its mixed effects, Avandia by itself is not likely to be helpful in treating lipoatrophy. However, the researchers suggested that combining Avandia with a drug that reduces fat breakdown could help increase fat stores in people suffering from lipoatrophy, providing a more effective treatment.

Avandia has also raised concerns recently that it might cause heart problems. However, there are similar drugs that are currently under development, such as rivoglitazone, which is currently in Phase 3 clinical trials.

For more information, please see the study in the journal Metabolism (subscription required).

Although the Food and Drug Administration (FDA) does not have to follow the recommendations of the advisory committee, it usually does.

Gardasil (Human Papillomavirus Quadrivalent (types 6, 11, 16, and 18) Vaccine, Recombinant) is a three-dose vaccine meant to protect against diseases caused by the human papillomavirus (HPV). HPV causes genital warts, up to 75 percent of cervical cancers, and up to 90 percent of anal cancers.

Currently, Gardasil is approved for the prevention of cervical cancer in women and genital warts in men and women.

The FDA advisory committee’s decision was based on results from an efficacy study conducted in 598 men, 16 to 26 years of age, who have sex with men. The trial showed that Gardasil was 78 percent effective in preventing precancerous anal lesions associated with HPV infection.

Although the trial was only in men aged 16 to 26, the advisory panel agreed with Merck’s argument that the results were likely to extend to boys aged 9 to 16 and women.

HPV is the most common sexually transmitted infection, with studies estimating that at least 50 percent of sexually active adults will contract genital HPV at some point in their lives. Most people who have HIV also have HPV.

Partly due to longer lifespans, anal cancer caused by HPV is increasingly a problem in people with HIV. HIV-positive adults are 30 to 50 times more likely to get anal cancer than people without HIV, and bisexual and homosexual men with HIV are up to 60 times more likely to get anal cancer. In addition, studies have shown that antiretroviral therapy does not reduce the risk of getting anal cancer.

To effectively prevent anal cancer, Gardasil must be given before HPV is contracted, preferably when a person has had little or no prior sexual contact. The vaccine is given as three injections over six months.

For more information, please see the press release on the Merck website.

Sulfasalazine (Azulfidine) is a fairly old drug that is used to treat the inflammation associated with Crohn’s disease and rheumatoid arthritis.

“This marks a new direction in which to look for new therapies to treat Pneumocystis as well as other inflammatory diseases,” said Professor Terry Wright, one of the authors of the study, in a press release.

Pneumocystis pneumonia (PCP) is caused by a yeast-like fungus. It can be a life-threatening illness in people with AIDS, cancer, or other diseases that compromise the immune system. Mortality rates of 50 percent or higher have been reported for AIDS patients with severe PCP.

Symptoms of PCP include fever, a dry cough, shortness of breath, weight loss, or a general feeling of illness. Symptoms can worsen rapidly or gradually over a period of weeks or months.

Although most people are infected with the fungus at some point in their lives, their immune systems usually keep Pneumocystis in check and do not allow it to multiply and cause disease.

People with weakened immune systems face a higher risk of developing PCP. For people with HIV, a CD4 (white blood cell) count less than 200 to 300 cells per microliter generally indicates a higher risk for PCP.

In addition, severe PCP can develop in people with HIV following successful antiretroviral therapy. This type of pneumonia is called PCP-related Immune Reconstitution Inflammatory Syndrome (PCP-IRIS).

Much of the damage in PCP is actually caused by a person’s own immune system trying to fight the fungus. Antiretroviral therapy can strengthen the immune system and cause it to attack the fungus, increasing lung injury and inflammation.

As a result, doctors commonly use a combination of two different types of drugs to treat PCP: an antibiotic to kill the PCP fungus and steroids or another type of drug to reduce the resulting inflammation.

However, there is little concrete evidence that steroids improve survival among people with PCP.

In this study, researchers set out to evaluate the effects of the anti-inflammatory drug sulfasalazine in mice with PCP-IRIS to see if it might be a viable alternative to steroids. All mice also received the antibiotic trimethoprim sulfamethoxazole (Septra).

As the researchers expected, results showed that sulfasalazine significantly decreased inflammation in the lungs.

In addition, the drug dramatically enhanced fungal clearance from the lungs of the mice.

Further investigation revealed that sulfasalazine activated macrophages in the lungs. Macrophages are a type of immune cell that engulfs and kills microbes. Results showed that 17 days after PCP infection, sulfasalazine-treated mice had nine times as many macrophages that had engulfed fungus particles compared to mice that received only antibiotics.

“This was unexpected,” said Professor Jing Wang, another author on the paper, in the press release. “It turns out that sulfasalazine actually results in a reduced fungal burden. The drug helps the body clear the infection.”

The researchers also measured lung compliance (the ability of the lungs to stretch during breathing) and lung resistance (the limitation of air flow to and from the lungs) over the course of the study to determine the severity of PCP-IRIS in the mice.

Results showed that mice that received sulfasalazine had significantly less lung damage over the course of the study. For example, by day 18, the mice showed a 19 percent decrease in lung compliance, compared to a 59 percent decrease in lung compliance in mice not treated with sulfasalazine.

In addition, the sulfasalazine-treated mice had recovered nearly normal lung function by day 25 of the study. They also lost less weight and were generally healthier than mice that were not treated with sulfasalazine.

The study results suggest scientists may be able to develop more effective treatments against PCP by simultaneously blocking inflammation while enhancing the body’s defense mechanism against the fungus.

However, the results need to be confirmed in people with HIV to ensure the beneficial effects of sulfasalazine hold in humans as well as in mice.

For more information, please see the article in PLoS Pathogens.

Based on the studies, the World Health Organization (WHO) has revised its recommendations on how to prevent mother-to-child transmission. The WHO now recommends that Kaletra (ritonavir/lopinavir)-based treatment be used for women and children with previous exposure to single-dose Viramune (nevirapine).

The results are geared primarily toward women in developing countries, where a single dose of Viramune is commonly used to prevent HIV transmission during childbirth. Viramune is easily available and relatively inexpensive, and it remains active in the blood for a fairly long time after being taken. This means a single dose during labor can be effective for several days.

After childbirth, it is common for Viramune to be included in general antiretroviral therapy, including for women who used single-dose Viramune during labor and for HIV-positive children who were exposed to Viramune during birth.

However, it is known that the single-dose Viramune used during labor can cause Viramune-resistant forms of the HIV virus to develop in both the women and their babies. It was not known whether this would affect their ability to take Viramune later on as part of their normal antiretroviral regimen.

In these two studies, researchers found that women and children who had been exposed to single-dose Viramune 6 months or more before beginning treatment did not respond as well to Viramune-based therapy as Kaletra-based therapy. Study participants who started with HIV resistance to Viramune were least responsive to Viramune-based antiretroviral therapy.

Antiretroviral Therapy In Women Exposed To Single-Dose Viramune

The first study investigated the efficacy of Kaletra-based therapy versus Viramune-based therapy in two groups of HIV-positive women: 241 women who had been exposed to single-dose Viramune 6 months or more prior to the start of the study, and 500 women who had no previous exposure to Viramune.

Participants were randomly assigned to receive either Viramune or Kaletra; both groups also received Truvada (emtricitabine/tenofovir).

Researchers then monitored the women for treatment failure, which is when antiretrovirals fail to suppress HIV replication.

Over the course of the study, researchers found that in the women who had been exposed to single-dose Viramune, 26 percent taking Viramune experienced treatment failure, compared to 8 percent of women taking Kaletra.

In contrast, in women with no prior exposure to single-dose Viramune, treatment failure occurred at the same rates in both the Kaletra and Viramune-based therapy groups (14 percent).

Within the single-dose exposed Viramune group, women who had HIV that was resistant to Viramune had the highest rates of treatment failure, 73 percent, compared to 19 percent among women without Viramune-resistant HIV.

However, the researchers found that women who had been exposed to single-dose Viramune longer ago were less likely to experience treatment failure while taking it. This suggests that women may be able to take Viramune if they wait long enough after being exposed during childbirth, but the researchers were uncertain how long women would need to wait.

Antiretroviral Therapy In Children Exposed To Single-Dose Viramune

Results were similar for a second study conducted in HIV-positive children. Children exposed to single-dose Viramune at birth responded better to Combivir (zidovudine/lamivudine) plus Kaletra than to treatment with Combivir plus Viramune.

The study involved 164 HIV-positive children, all of whom had been exposed to single-dose Viramune. The children were randomly assigned to take either Viramune plus Combivir or Kaletra plus Combivir.

In this case, researchers noted rates of treatment failure in the children over a period of 6 months.

Results showed that almost 40 percent of children in the Viramune group experienced treatment failure, compared with 22 percent in the Kaletra group.

As with the women, Viramune resistance significantly increased the likelihood of later Viramune treatment failure; 83 percent of children with HIV resistant to Viramune failed treatment containing Viramune, compared with 36 percent of children who did not have Viramune resistance.

The authors of both studies recommended that women and especially children who have been exposed to single-dose Viramune avoid subsequent antiretroviral therapy containing Viramune.

The authors also emphasized that new, inexpensive mother-to-child HIV prevention strategies and treatments are essential. Kaletra is significantly more expensive than Viramune and is not as easily taken by children.

For more information, please see the studies and a companion article in The New England Journal of Medicine.

“Our work…suggest[s] that more clinical trials should be aimed at comparing early-treated and chronic-treated patients by a variety of different immunologic parameters,” said Dr. Susan Moir, lead author of the study, in correspondence with The AIDS Beacon.

The findings shed light on a group of immune cells called B cells and how early initiation of antiretroviral therapy (ART) may help prevent irreversible damage to the immune system.

B cells are a type of immune cell. They make antibodies, proteins that help the immune system identify and fight infectious pathogens like bacteria and viruses.

Memory B cells are a special type of B cell that are formed after infection with a pathogen. Their role is to remember how to make antibodies to that particular kind of virus or bacteria.

Memory B cells are the reason a person who catches an illness, like the chicken pox, becomes immune to it thereafter. Vaccines work by prompting memory B cells to make antibodies to the virus or bacteria from the vaccine, creating immunity.

In contrast, “exhausted” B cells are nonfunctional and cannot produce antibodies.

In this study, scientists measured the amount and type of B cells in blood samples taken from three groups of men. The first (“early treatment group”) contained men who had been HIV positive for six months or less and had not yet started ART. The second group (“late treatment group”) had been HIV positive for a while, in some cases several years, but had also not yet started ART. The third group contained men who were HIV negative.

At the start of the study, all the men who had HIV started taking antiretroviral therapy.

Results showed that at the start of the study, both groups of HIV-positive men had fewer B cells in their blood than the HIV-negative men. Once the two groups of HIV-positive men began ART, the number of B cells in their blood began to rise in a similar manner.

However, the types of B cells in the two HIV-positive groups differed significantly throughout the study.

Men who started antiretroviral therapy early were able to achieve numbers of memory B cells similar to those in HIV-negative men; men who started treatment late, however, continued to have low levels of memory B cells. Furthermore, men who started treatment late had greater numbers of immature B cells, while men who started ART early were able to reduce their levels of undeveloped B cells to those of HIV-negative men.

The late-treatment group also had significantly more exhausted B cells than the other two groups of participants, even after one year of ART.

To investigate how these differences in the types of B cells present affected the immune system, researchers also examined how the two groups of HIV-positive men responded to an influenza vaccine at the start of the study and one year after beginning ART.

Results showed that one year after starting antiretroviral therapy, men who had started treatment early had a greater number of B cells that successfully made anti-influenza antibodies compared to the late-treatment group.

This suggests that starting antiretroviral therapy early in the course of HIV infection allows patients to better fight off other infections than if they start ART later.

Dr. Moir said follow-up studies are planned but noted that it is difficult to find eligible participants. Most people who have had HIV for a while stay current on their vaccines, while those who have just been diagnosed usually receive the vaccines when they start ART.

“[This] means we cannot measure the before and after effects of ART on vaccination response,” said Dr. Moir.

“We are nonetheless continuing to investigate these questions and trying to find simpler schemes. We also continue to measure responses to HIV itself, which also differed between the two groups,” she added.

The idea of starting ART early is a controversial one, due to possible long-term side effects of antiretroviral drugs. A different clinical trial testing the effects of starting HAART when a person’s CD4 (white blood cell) count drops below 500 cells per microliter – earlier than the current recommendation of 350 cells per microliter – is currently underway.

The study, named Strategic Timing of Antiretroviral Treatment (START), is a joint effort by the University of Minnesota, the National Institutes of Health, various European HIV institutes, and several pharmaceutical companies.

The study is currently recruiting participants.

For more information, please see the study in the journal Blood (abstract). For more details on the START study, please see the clinical description at the United States Clinical Trials registry.

October 15 Is National Latino AIDS Awareness Day – October 15 marks the eighth National Latino AIDS Awareness Day. Its purpose is to raise awareness of the impact of HIV and AIDS on the Latino community, with a focus on prevention and HIV testing efforts for Latino men and women. In a statement commemorating the day, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, noted that Latino men and women have the second highest death rate from HIV and AIDS of all ethnic groups. He also recognized the high clinical trial participation rates for Latinos, which help bring new research and treatments to the HIV/AIDS population. For more information, please see the National Latino AIDS Awareness Day website.

NIAID To Hold Public Meeting On Restructuring Its HIV/AIDS Clinical Trial Networks – The National Institute of Allergy and Infectious Diseases (NIAID) is hosting a public meeting on October 26 in Arlington, VA to discuss the future of the organization’s clinical trial networks. NIAID seeks to expand its networks to include clinical research on other major infectious diseases, including tuberculosis and hepatitis, that are common in people with HIV. Discussion will center on expectations for the networks, possible changes in structure, research priorities, collaborative opportunities, and information about the upcoming application process. Presently, NIAID supports six HIV/AIDS networks; their funding expires in 2013 and 2014. For more information or to register to attend the meeting, please see the NIAID website.

United States Pledges $4 Billion For Global Fund To Fight HIV/AIDS – The Obama Administration announced last week that it will support the Global Fund to Fight AIDS, Tuberculosis, and Malaria by contributing $4 billion over the next 3 years. However, the Administration also called for reforms to the Fund in specific areas, such as grant management and accountability, more effective investments, and increased contributions from other donor nations. The Fund provides prevention efforts and treatment for people living in low-income countries. For more information, please see the U.S. Department of State website.

For a more detailed listing of HIV/AIDS related events, please check the AIDS Beacon Events Calendar.

Arizona Considers Legalizing Medical Marijuana – Voters in Arizona will decide November 2 whether to legalize medical marijuana in the state. Proposition 203 would allow licensed physicians in Arizona to recommend the drug to patients with certain medical conditions, including HIV/AIDS. This is the fourth attempt to legalize medical marijuana in Arizona. Medical marijuana is not currently approved by the United States Food and Drug Administration, but several states have legalized it to provide relief for patients with serious illnesses. For more information, please see the article on The Arizona Republic website.

Governor Paterson Vetoes Rent Relief For AIDS Patients In New York – Governor David Paterson vetoed a bill last week that proposed additional rent subsidies for approximately 11,000 New Yorkers with HIV/AIDS. Under the terms of the bill, people who receive housing assistance from New York’s HIV/AIDS Services Administration would have had to spend no more than 30 percent of their income on rent. Paterson vetoed the bill because he believes it would strain New York’s tight finances. Paterson stated that he will support the bill if the Legislature makes clear how the costs, estimated at $20 million, would be covered. For more information, please see the article on The New York Times website.

Language Impairments Are Not More Common In HIV-Positive Children

This study found that language impairments are no more common in HIV-positive children than in HIV-negative children who have been exposed to HIV and have a similar background.

Language impairment is common in children infected with HIV at birth and often occurs together with cognitive and hearing impairments. However, researchers have been uncertain whether HIV causes developmental problems or if children with HIV are more likely to have impairments because of their socioeconomic backgrounds.

To see if HIV itself causes language problems in children, researchers studied 258 HIV-positive children and 115 children who were HIV negative but had been exposed to HIV. Most of the children were African American (72 percent) or Hispanic (24 percent).

Results showed that children with HIV were not at greater risk of language impairment, with 35 percent of the HIV-positive children and 39 percent of the HIV-negative children diagnosed with language difficulties.

Instead, language problems were associated with ethnicity and the parents’ education levels. The researchers attributed this to the effects of family and socioeconomic factors on language development.

However, since all the children had been exposed to HIV, the researchers could not eliminate this as a risk factor.

Disclosing HIV Status To HIV-Positive Children And Teens

In this Ugandan study, researchers investigated when and how HIV-positive children and teenagers thought they should learn their HIV status. The study also examined the impact of this information on the children and their families.

The study included 187 HIV-positive children between 5 and 19 years old who were interviewed about when and how they had been told they were HIV positive. All contracted HIV by mother-to-child transmission and already knew their HIV status.

Researchers found that children and teens with HIV seemed to quickly accept their HIV status and generally handled the diagnosis very well.

Most of the participants (59 percent) said they were happy with the timing of their disclosure. Children generally wanted to be told their status by close relatives; half said they preferred to learn they were HIV positive from their mothers.

After learning their HIV status, 45 percent of the children and teens reported having felt nothing, while the rest reported short-lived feelings of fear, sadness, anger, or confusion.

Most of the children (77 percent) did not tell others their HIV status following disclosure because of the stigma associated with HIV and AIDS.

In general, parents and guardians also said they were satisfied with the results of disclosure.

The children and teens in the study recommended that HIV-positive children be told their status by 10 years of age.

The researchers supported this recommendation and concluded that the benefits of disclosure to HIV-positive children and teens outweigh the fears of parents and health workers.

New York State And Johns Hopkins Release Guidelines On Disclosure Of HIV Status To Children And Teens

The New York State Department of Health AIDS Institute and Johns Hopkins University announced the release of disclosure guidelines at AIDS 2010 for telling HIV-positive children and teenagers their HIV status.

The researchers emphasized the importance of follow-up to make sure children receive the necessary support after learning their status. The guidelines suggest using age-appropriate and truthful explanations of HIV and AIDS, discussing the child’s concerns about HIV, and clarifying any misconceptions.

They also emphasized that ongoing support is essential for children and teens to adjust well to life with HIV. The researchers advocate for disclosure as an ongoing process with continuing discussions as the child matures, rather than a one-time event.

New York is working on distributing the guidelines more widely to clinicians and caregivers for HIV-positive children and teens.

For more information, please see the AIDS 2010 conference website.

“The positive effect of micronutrient supplements in HIV patients goes beyond their positive effect on the immune system,” said Dr. Marianna Baum, Professor of Dietetics and Nutrition at Florida International University Stempel School of Public Health, in email correspondence with The AIDS Beacon.

“They improve mood, depression, quality of life, energy levels, capacity to exercise, and [illnesses] among other factors of daily living,” she added. Dr. Baum was the lead researcher on the studies.

The supplements in the studies contain micronutrients, which are vitamins and minerals that the body needs in very small amounts to produce enzymes, hormones, and other substances necessary for growth and development.

Although two of the studies are small and need to be confirmed by larger studies, results suggest that specific micronutrients may help improve immune system health of people living with HIV/AIDS.

Micronutrient Supplements May Slow HIV Disease Progression

The first study investigated whether micronutrient supplementation could improve immune function and delay the onset of AIDS in HIV-positive adults in Botswana. Results showed that supplementation with micronutrients was safe and significantly delayed the progression of HIV to AIDS.

The study enrolled 875 HIV-positive adults and was carried out over 24 months. Participants started with CD4 (white blood cell) counts greater than 350 cells per microliter. None were on antiretroviral therapy.

Participants were randomly assigned to receive either a placebo or a nutritional supplement containing vitamin B-complex, vitamins C and E, and selenium. Researchers then monitored the participants’ HIV disease progression by tracking their CD4 cell counts.

Participants whose CD4 counts dropped below 250 cells per microliter were diagnosed as having progressed to AIDS and were started on antiretroviral therapy.

Results showed that over the two-year study period, taking micronutrient supplements reduced the probability of a participant’s CD4 count falling below the 250 threshold by 38 percent.

The researchers concluded that supplements may increase the amount of time before people with HIV show symptoms or need to start antiretroviral therapy.

Additional studies are currently in progress on the effect of micronutrient supplementation on illness and mortality rates in people with HIV.

Zinc May Help Prevent Immune System Failure In HIV-Positive Adults

Results from this small study suggest that zinc supplementation is safe and may help prevent immune failure in HIV-positive adults on antiretroviral therapy.

Zinc is an important micronutrient that the body requires to develop CD4 cells and activate the immune system. Zinc is naturally found in beans, nuts, whole grains, and certain types of seafood, but can also be taken as a supplement in pill form.

Immune system failure occurs in people with HIV when their CD4 cell count is too low to protect the body from infection. When this happens, patients are at a greater risk of disease progression and death.

For the study, researchers monitored 40 HIV-positive adults who were on antiretroviral therapy and had achieved viral suppression (viral load, or amount of virus in the blood, of 50 copies per milliliter or less).

Participants were randomly assigned to receive either a zinc supplement or a placebo. CD4 cell counts and viral loads were monitored over 18 months. Immune system failure was defined as having a CD4 count of 200 cells per microliter or less.

By the end of the study, four participants in the placebo group (21 percent) experienced immune system failure. None of the participants taking zinc supplements experienced immune system failure.

The researchers concluded that zinc supplements may help maintain immune system health when taken with antiretroviral drugs. However, long-term studies with more participants are still needed to conclusively assess the benefits of zinc supplementation in people with HIV.

Antioxidants May Improve Immune Health And Reduce Mitochondrial Damage

This small study found that taking antioxidants may help improve immune system health and reduce mitochondrial damage.

Mitochondria are the power centers of cells. They provide the energy that cells need to move, divide, and perform other functions. HIV infection and long-term antiretroviral therapy have been associated with mitochondrial damage.

Antioxidants can help prevent damage to cells and mitochondria by scavenging free radicals – highly reactive chemicals that can damage DNA, proteins, and other biological molecules. Antioxidants are found in many fruits, vegetables, nuts, and some meats.

The purpose of this study was to see if antioxidants could help improve immune function and prevent mitochondrial damage in people with HIV who are taking antiretroviral drugs.

The study involved 25 HIV-positive adults on antiretroviral therapy. Participants were randomly assigned to receive either an antioxidant supplement or a placebo for 8 weeks. The supplement contained vitamin B-complex, vitamins C and E, zinc, selenium, N-acetyl cysteine, and α-lipoic acid.

Both groups were evaluated at the beginning and end of the study to gauge changes in CD4 count, viral load, mitochondrial damage, insulin levels, and body size and proportions.

Results showed that participants taking antioxidants had reduced mitochondrial damage compared to participants taking a placebo.

They also had small increases in the proportion of CD4 immune cells and small decreases in insulin resistance, although these were too small to be significant in this small study. There were no safety issues observed with the supplements.

The researchers concluded that antioxidants may help with immune system recovery and reduce mitochondrial damage in HIV-positive adults. However, long-term studies with more participants are still needed to confirm the benefits of antioxidant supplements in people with HIV.

For more information, please see the AIDS 2010 conference website.

Two of the studies focused on rates of cancers, particularly non-AIDS-defining cancers, in people with HIV and AIDS.

AIDS-defining cancers are cancers that are common in people with advanced HIV infections as a result of their weakened immune systems. Although they can appear in people who are HIV-negative, the development of these cancers in a person with HIV is closely tied to the health of the immune system. As a result, a person with HIV who has an AIDS-defining cancer is usually classified as having AIDS.

In contrast, developing a non-AIDS-defining cancer does not lead to a diagnosis of AIDS. Non-AIDS-defining cancers are in some cases more common in people with HIV than in the general population, but can occur even in people who carefully control their HIV infection.

Antiretroviral therapy has significantly improved the health and survival of people living with HIV. As a result, the rates of AIDS-defining cancers such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma have decreased.

However, longer lifespans increase the risk for non-AIDS-defining cancers. As people with HIV survive longer with antiretroviral therapy, non-AIDS-defining cancers, which develop over a long time period, become more common.

In general, studies presented at AIDS 2010 found that the rate of non-AIDS-defining cancers among people with HIV and AIDS has increased rapidly, with HIV-positive individuals generally being diagnosed with such cancers at an earlier age than HIV-negative adults.

Two additional studies showed that Selzentry (maraviroc) is not associated with a higher risk of cancer and that switching to Isentress (raltegravir) during chemotherapy may allow cancer patients to safely receive full-dose chemotherapy.

Non-AIDS-Defining Cancers Are Increasing In People With AIDS

A study from the National Cancer Institute and the Centers for Disease Control (CDC) presented an estimation of the number of cancers over time in the U.S. AIDS population.

According to the study authors’ estimations, the number of AIDS-defining cancers decreased and the number of non-AIDS-defining cancers increased significantly among people with AIDS. Researchers attributed these changes to the growth and aging of the AIDS population and increased rates of certain cancers.

The researcher analyzed data from the CDC and cancer registries across the United States, and found that the share of adults aged 50 years or older increased from 8 percent of the population with AIDS in 1991 to 29 percent in 2005.

During the same period, AIDS-defining cancers, mainly Kaposi’s sarcoma and non-Hodgkin’s lymphoma, decreased 75 percent from 7,284 cases in 1993 to 1,736 cases in 2005.

In contrast, non-AIDS-defining cancers increased nearly six-fold from 416 cases in 1991 to 2,437 cases in 2005. Anal cancer and prostate cancer had the largest increases, with 20-fold and 12-fold increases in the number of cases, respectively.

Rates of lung cancer and Hodgkin’s lymphoma remained fairly stable.

The researchers also estimated that 4,388 cases of cancer occurred between 2004 and 2007 among people from 34 states who were HIV-positive but did not have AIDS. This included 892 cases of lung cancer, 381 cases of anal cancer, and 327 cases of Hodgkin’s lymphoma.

However, the researchers did not indicate if these numbers were increasing or decreasing over time.

The researchers emphasized that “cancer prevention and treatment in HIV-positive persons is increasingly important.”

People With HIV Get Non-AIDS-Defining Cancers Earlier And More Often

Another study examined the rate of cancer and age at cancer diagnosis in patients at an HIV clinic in Atlanta. Researchers found that many non-AIDS-defining cancers occurred at higher rates and at an earlier age in people with HIV compared to the general Atlanta population.

From 2000 to 2007, 512 clinic patients were diagnosed with cancer. Of these, 62.5 percent had AIDS-defining cancers and 37.5 percent had non-AIDS-defining cancers.

On average, the age of HIV-positive patients at cancer diagnosis was 42 years old. Except for Hodgkin’s lymphoma, all non-AIDS-defining cancers occurred earlier in the HIV-positive clinic population than in the general population.

Breast cancer occurred in the HIV-positive population an average of 7 years earlier than in the general Atlanta population. Liver cancer was diagnosed an average of 16 years earlier.

Additionally, cancer rates in people with HIV were much higher compared to the general Atlanta area population, except for prostate cancer and breast cancer. Lung cancer occurred 4.5 times more often than expected, after taking into account age, race, and gender; Hodgkin’s lymphoma occurred 20 times more often than expected, and anal/rectal cancer occurred 68 times more often.

The researchers reported that the clinic patients in general had fairly advanced HIV infections. Of those diagnosed with non-AIDS-defining cancers, average CD4 (white blood cell) counts were 263 cells per microliter for men and 344 cells per mcroliter for women.

Only 17 percent of the men and 11 percent of the women had undetectable viral loads (amount of virus in the blood) at the time of their cancer diagnosis.

The researchers did not determine whether the low CD4 counts and high viral loads played a role in the rate of cancer occurrence.

The scientists concluded that people with HIV should consider cancer screening earlier than the general population.

Selzentry Does Not Increase Cancer Risk

A study sponsored by Pfizer, the maker of Selzentry, reported the rate of cancer development for treatment-naïve and treatment-experienced clinical trial participants taking Selzentry. Results showed that participants in the Phase 2b/3 trials were not more likely to get cancer from taking Selzentry.

Selzentry belongs to a relatively new class of antiretrovirals called entry inhibitors. Entry inhibitors work by preventing HIV from entering and infecting human cells.

Although approved for use in treatment-experienced patients in 2007 by the U.S. Food and Drug Administration, there were concerns that Selzentry might cause cancer because of the unique way it works, which is different from other antiretroviral drugs.

To see if people taking Selzentry are actually at higher risk of developing cancer, researchers analyzed tumors reported in studies involving both treatment-experienced and treatment-naïve HIV-positive trial participants. A total of 1,499 patients were given Selzentry, 361 patients received Sustiva (efavirenz), and 270 received a placebo.

Cancer rates were similar for patients given Selzentry to rates for patients given Sustiva or the placebo. Rates of AIDS-defining cancers ranged from 0.6 percent to 1.6 percent of participants taking Selzentry, versus 0 percent to 2.4 percent of participants taking Sustiva or a placebo.

Rates of non-AIDS-defining cancers ranged from 0.8 percent to 3.6 percent for participants taking Selzentry, versus 1.6 percent to 2.5 percent for participants taking Sustiva or a placebo.

In all cases, these differences were not large enough to be significant.

Researchers also found that older age was associated with higher overall risk of tumor development in both treatment-experienced and treatment-naïve patients.

Isentress-Based HAART Is Safe And Effective During Chemotherapy

A small study investigated the safety and efficacy of Isentress-based HAART in HIV-positive patients treated for lymphoma with chemotherapy. Results showed that Isentress is effective in patients receiving chemotherapy and patients can receive full-dose chemotherapy while on Isentress.

In the past, doctors have worried about drug interactions between antiretrovirals and chemotherapy drugs. As a result, HIV-positive cancer patients often temporarily stop antiretroviral treatment while undergoing chemotherapy or take a reduced dose of chemotherapy drugs.

However, both of these adjustments can affect a patient’s health, either by allowing HIV to multiply again or by limiting the effectiveness of the chemotherapy.

Since Isentress is an integrase inhibitor, a relatively new class of antiretroviral drugs that work differently than most antiretrovirals, researchers thought Isentress may be safe even during chemotherapy.

To test this hypothesis, researchers examined nine patients treated for lymphoma with Isentress-based HAART and chemotherapy at the Centre hospitalier de l’Université de Montréal between May 2008 and December 2009.

Of the nine patients studied, seven had non-Hodgkin’s lymphoma and two had Burkitt’s lymphoma. Four patients were treatment-naïve, four patients had already achieved viral suppression with another antiretroviral regimen, and one patient had started antiretroviral treatment but still had a detectable viral load.

During chemotherapy and treatment with Isentress, eight of the nine patients achieved or maintained undetectable viral loads. Three months after chemotherapy, seven of the nine patients had survived (78 percent); two died due to progression of their lymphoma.

None of the patients developed antiretroviral treatment-related side effects during the chemotherapy.

The researchers concluded that Isentress can be used safely and effectively with full-dose chemotherapy for treatment of lymphoma.

For more information, please see the AIDS 2010 conference website.

By the end of this year, an estimated 25 million children around the world will have lost one or both parents to AIDS, including thousands of children in the U.S. At the end of 2008, nearly 2.1 million children were living with HIV worldwide. With the current economic recession, children affected by HIV now need more help than ever.

International Adoption Rates Are Dropping

Although there is little data available on adoption of HIV-positive children, comparisons of overall international adoption numbers suggest rates are dropping.

According to the U.S. Department of State, the number of international adoptions into the U.S. has been decreasing steadily since 2004, with a total of 12,753 adoptions occurring in 2009 compared to a high of 22,990 in 2004.

From 2005 to 2009, the top four countries from which children were adopted were China, Russia, Guatemala, and Ethiopia, three of which have relatively low adult prevalence rates for HIV/AIDS. Ethiopia’s prevalence rate, the highest of the four at 2 percent, is still fairly low compared to many African nations.

In India, recent reports have claimed that adoption centers were unable to find families willing to adopt HIV-positive children, and as a result, no HIV-positive children were adopted in India from 2008 to 2009.

In 2009, a Moscow orphanage specializing in children of HIV-positive parents reported that it adopted out 31 children, many of them HIV-positive. However, this was down from a high of 49 children in 2007.

In many African countries, the number of AIDS orphans comprises at least half of the total number of orphans in the country. Such a large number of orphans has taken a heavy toll on communities, where traditional family structures to take care of orphans have broken down.

A study in Zambia in 2002 found that 63 percent of households surveyed were caring for orphans or children who were considered high-risk due to a parent’s illness or poverty. More than half of orphans had been separated from their siblings.

Without parents and a stable home, studies have shown that these children are more likely to suffer long term emotional consequences, such as depression, anxiety, and anger.

In addition, lack of parents to provide an income may drive young children to skip out on education and search for work instead, making them more vulnerable to exploitation and abuse.

International Adoption Of HIV-Positive Children

When Margaret Fleming formed Chances By Choice in 2003 to help place children with HIV with adoptive parents, many were skeptical of the idea.

To date, however, the organization has placed over 60 HIV-positive children with families. Fleming herself has adopted three HIV-positive children, both domestically and internationally, and has no regrets about the process (see related Beacon news).

Children with HIV, she said, are often easier to care for than children with diabetes.

With the lifting of the HIV travel ban (see related Beacon news), bringing HIV-positive children into the U.S. has become easier. Additionally, HIV-positive children are often considered special needs, so countries may ease regulations to facilitate their adoption.

Nonetheless, international adoptions can be long, expensive, and difficult.

International adoptions must comply with three different sets of laws: U.S. federal laws, the state laws of the adopting family, and the laws of the child’s country of birth.

Many countries have regulations about an adoptive parent’s age, marital status, and marriage length.

In Ethiopia, for example, couples usually must be married for at least 5 years prior to adopting, and there can usually be no more than a 40-year age difference between the adopting parents and the child. Gay or lesbian parents are not allowed to adopt in Ethiopia.

Certain requirements may be relaxed, however, for couples wanting to adopt children with HIV/AIDS. In Ethiopia, for example, single women may be allowed to adopt HIV-positive children.

Children with two HIV-positive parents, or only one living HIV-positive parent, are routinely considered orphans by the government of Ethiopia, which then becomes their legal guardian. Orphans are eligible for adoption after living at an orphanage for three months.

According to the Department of State, as of January of this year, “HIV infection is no longer an inadmissible condition [for entry into the U.S.], and HIV testing is no longer required for medical examinations for visa purposes.”

Since a special waiver is no longer necessary to bring an HIV-positive child into the U.S., a family wishing to adopt an HIV-positive child can complete the adoption in the same manner as any other international adoption.

The entire process usually takes one to four years, though it can take longer. Those wishing to adopt internationally must travel to the country for a period of time, ranging from a few days to several weeks.

The cost of an international adoption varies greatly; adoption services can cost as much as $30,000 per case.

For HIV-positive children, however, financial assistance may be available. For example, Promise Child Grants are currently available to parents adopting HIV-positive children age 2 years or older from Ethiopia. The grants provide $6,000 of financial assistance to eligible families.

The U.S. government also offers a tax credit for adoption of children, internationally or domestically. The credit, up to $13,170 per child for tax years 2010 and 2011, covers eligible out-of-pocket expenses for the adoption. Families who adopt a special needs child can claim the entire credit, even if their out-of-pocket expenses were less than the full credit amount.

Adoption Of HIV-Positive Children In The U.S.

For some people, making a difference in the lives of children with HIV starts closer to home. An estimated 200 children are born with HIV in the U.S. each year, and many more children enter the foster care system after losing parents to the virus.

When foster mother Lisa Bushman first met Olivia, she was three years old and HIV positive. At first, Bushman was not bothered by the fact that Olivia had HIV.

“I did think about it later,” she said. “I had a 13 month old little boy living with me at the time as well, and admittedly the first night she was in my home I had doubts.”

After researching the disease, however, Bushman recalls feeling relieved and excited at the prospect of having Olivia in her home.

She adopted Olivia by the time she was six years old.

Now an eight year old, Olivia takes a “cocktail” of three HIV medications every 12 hours. She also takes additional pills every 12 hours to control a seizure disorder she developed in 2008.

Other than that, “Olivia is by far my healthiest child of my three,” said her mother. “She is rarely sick, with an occasional cold or sore throat. We rarely have to go to her local pediatrician at all. It is quite ironic!”

Initially, as Bushman went through the process of adopting her three children, she used her blog, Little Did I Know, as a way to keep friends and family up to date on her experiences. Over time, she developed a community of supporters who were going through the same things she was.

As a summer project, she allowed Olivia to begin writing her own blog as well.

“I really didn’t guide her at all with what she wanted to name her blog (HIV – Heroes Inspiring Vision) or what she wanted to talk about on her blog, but I did know that she has some wonderful views of people and the world and hoped that maybe some of that would come through her writing. I thought this could be a great way for others to see that people with HIV are living and working and playing and creating and thriving among ‘us,’” said Bushman.

“I think she has been pleasantly surprised that so many people are interested in reading her words and watching her journey,” she added.

When Olivia was still her foster child, Bushman was not able to disclose Olivia’s HIV status to others. After becoming her mother, however, Bushman was faced with the tough decision of whether to tell others.

According to Bushman, “It wasn’t much of a decision. I never want Olivia to question who she is because of three little letters. As she says on her blog, ‘I’m just like everyone else, just with different blood.’ On the day of her adoption, I sent many letters to friends and family, feeling that was the best way to let everyone ‘in on it’ at once. We have been extremely blessed to have thus far received no negative responses from my letter.”

Through her blog and experiences with adopting an HIV-positive child, Bushman feels that more people are becoming open to adopting children with HIV. Although many still remember HIV for what it was in the 80s, Bushman hopes “millions more open their eyes to the very real picture of HIV, that of a thriving, beautiful, non-threatening eight-year-old girl.”

Resources On Adopting HIV-Positive Children

Many organizations exist throughout the U.S. that help parents adopt HIV-positive children.

Adoption-Link, an adoption agency located in Chicago, hosts a program entitled Chances by Choice that facilitates the domestic and international adoption of HIV-positive children.

Positively Orphaned, an online blog, features children waiting to be adopted. In addition, the website provides stories from families who have adopted children with HIV as well as links to information regarding HIV and adoption.

The Children’s Place, another organization located in Chicago, aids families and children affected by HIV by helping them find shelter, providing education and daycare services to young children, and providing counseling services to families. In addition, the Children’s Place has a foster care program and also facilitates the domestic adoption of HIV-positive children.

Positively Blessed is a blog written by a mother of two girls, one of whom is HIV positive and was adopted internationally. The blog details her experiences with adoption, as well as everyday life raising a child with HIV.

For more information on adoptions, please see the U.S. Department of State website or the Adoptions.com website. For information on the adoption tax credit, please see the IRS website.

Therapeutic HIV vaccines work by enhancing the body’s natural immune response, helping to control HIV in people already infected with the virus.

This is in contrast to preventative vaccines, which are used in HIV-negative individuals to prevent infection.

Researchers hope therapeutic vaccines will decrease dependence on antiretroviral drugs, which must be taken for life and often have serious side effects.

“A vaccine that enhanced the body’s ability to control HIV and delayed or decreased the dependence on anti-HIV drugs would be a major breakthrough for HIV treatment,” said Dr. Melanie Thompson, a lead investigator of one of the HIV vaccine trials.

No therapeutic vaccines are currently approved by the United States Food and Drug Administration.

DNA Vaccines

DNA vaccines contain pieces of DNA into which copies of several viral genes have been inserted. When human cells take up the DNA, they produce proteins encoded in the viral genes.

Researchers hope that the body’s immune system will recognize these proteins as harmful foreign agents and mount a powerful protective response.

DNA vaccines are a relatively new idea, and their effectiveness has not been well studied yet, although preliminary clinical trials have usually found them to be safe.

A small Phase 1 clinical trial investigating a therapeutic HIV DNA vaccine from GeoVax Labs is currently recruiting participants (pdf).

To be eligible for the GeoVax study, participants must have begun antiretroviral treatment within six months of diagnosis with HIV/AIDS. Additionally, individuals who have been HIV-positive for up to six months, but are yet to begin treatment, may be eligible for enrollment in the study.

Participants will be monitored to determine the safety of the vaccine and strength of their immune response for up to 77 weeks. For this initial study, only 10 to 12 people will be enrolled in the trial.

So far, studies in HIV-positive primates treated with the vaccine soon after infection gave good results. Clinical trials will now see if these results extend to HIV-infected humans as well.

Another Phase 1 DNA vaccine trial is also currently recruiting participants in London.

This trial, run by the Imperial College London and the Medical Research Council, will test a new therapeutic DNA vaccine coupled with immune-based therapy, which includes hormones and proteins called cytokines.

Immune-based therapies could help patients’ immune systems fight viruses on their own. Hormones and cytokines help regulate the immune system and can be used to induce, or prevent, growth and activity of particular cells in the immune system.

The researchers are especially interested in “why some people with HIV progress more slowly to disease and have longer survival without highly active antiretroviral therapy (HAART) than others.”

Their goal is to see if the vaccine plus immune-based therapy can create long-term nonprogressors, who are able to control the HIV virus for long periods of time without antiretrovirals.

The trial began in September 2009 and will investigate the safety and efficacy of the vaccine plus immune-based therapy for 52 weeks in approximately 30 HIV-positive individuals.

Study participants must be aged 18 or over with viral loads of less than 50 copies/milliliter and more than 400 CD4 cells/microliter.

Dendritic Cell Vaccines

Another novel vaccine type that will be tested in several new clinical trials is a dendritic cell vaccine, which is prepared using the participant’s own cells. Dendritic cell vaccines are considered to be very promising, because they are somewhat customized to each person.

To make a dendritic cell vaccine, researchers collect blood from participants and isolate a certain type of immune cell called a dendritic cell.

After exposing the cells to HIV proteins to prompt an immune response, the cells are reinjected into the study participant in hopes that they will now be activated and fight against HIV.

A Phase 1/2 clinical trial run by the University of Pittsburgh and the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) is currently recruiting participants.

Eligible candidates must be at least 18 years of age with CD4 cell counts of at least 350 cells/microliter and HIV RNA levels between 5,000 and 100,000 copies/milliliter. Participants must also be antiretroviral therapy naïve.

Baylor Research Institute along with Baylor University and the ANRS are also organizing a Phase 1 clinical trial to assess the safety and efficacy of a dendritic cell vaccine in HIV patients on HAART.

The study, which began in November 2008, is currently recruiting participants and enrollment is estimated at 19 patients.

Participants must be 18 years or older and must have been on HAART for at least 12 months prior to enrollment. Additionally, participants must have CD4 cell counts of at least 500 cells/microliter and HIV RNA levels no greater than 50 copies/milliliter.

Protein Vaccines

Finally, there is a more traditional vaccine trial that is currently recruiting HIV-positive participants in Italy. Traditional HIV vaccines contain virus proteins that are injected into the participant in hopes of increasing immune response to the virus.

The Phase 2 trial in Italy will evaluate the safety and efficacy of an HIV Tat vaccine. Tat is an HIV protein released by infected cells that increases the rate of replication of the virus.

The study was initiated by the Instituto Superiore di Sanita in September 2008 and will enroll about 160 participants.

Participants must be between the ages of 18 and 55, must not possess anti-Tat antibodies, and must be on successful HAART with HIV viral concentrations of less than 50 copies/milliliter and at least 200 CD4 cells/microliter.

The trial will measure immune responses to the Tat protein in participants for 144 weeks, or about two and a half years.

For more information on therapeutic vaccine clinical trials, please see the United States Clinical Trial Registry.

The test is used by doctors to measure HIV viral loads, or the amount of virus present in the bloodstream. The FDA states that the problem causes an error that prevents the test from giving results.

The FDA advised customers to discontinue use of lot M02635, with an expiration date of June 30, and to contact Roche Molecular Diagnostics Technical Support. The catalog number for the affected lot is 03155935018.

The Cobas Amplicor HIV-1 Monitor Test, cleared by the FDA in 2003, is a type of polymerase chain reaction (PCR) test used to measure viral load. It works by amplifying and measuring the amount of HIV RNA (HIV genetic material) in blood samples.

Together with CD4 cell counts, the test provides a baseline measurement that shows how actively the HIV virus is replicating.

A low test result indicates that the HIV virus is not actively multiplying, meaning that the risk of disease progression is low. A high result indicates that the virus is replicating and the disease is likely to progress faster.

Measuring viral loads and CD4 counts allow doctors to determine when patients should start antiretroviral treatment, and to monitor how well antiretrovirals are working for people already taking them.

Although different PCR tests are available, the different test methods often give different results for the same patient blood sample. Therefore, patients should use the same kind of test to measure viral load over time.

For more information, please see the press release on the FDA website.

Patrick Burke, Vice President of Corporate and Business Development at Myriad Pharmaceuticals, stated in an interview with The AIDS Beacon that Myriad is currently looking for a partner to advance MPC-4326 and an additional novel HIV drug. This partner would then acquire rights to advance the drugs further.

Myriad’s Phase 2 clinical trial into the efficacy and safety of MPC-4326 was terminated June 10.

MPC-4326 is an investigational drug that is a viral maturation inhibitor. The first in a new class of drugs, MPC-4326 prevents the HIV virus from maturing correctly by blocking a necessary enzyme, leaving the virus harmless.

Preclinical studies indicated that the drug is effective against strains of the HIV virus that are resistant to approved antiretroviral drugs.

In early clinical trials MPC-4326 did not pose any safety risks and successfully decreased the amount of HIV virus in the blood of HIV-positive participants.

The company stated in its press release that the focus on anti-cancer drugs is an effort to “conserve its financial resources to extend [Myriad's] projected cash runway beyond 2013,” indicating that the move away from anti-HIV drugs is for financial reasons rather than problems with safety or efficacy.

As of June 14, information on MPC-4326 had been removed from Myriad’s website, although cached versions were still available.

Studies indicated a slow rate of development of viral resistance to MPC-4326, which suggests it could be especially useful in HIV treatment. As viral resistance to approved drugs becomes more common, Myriad hoped MPC-4326 would prove effective in combination with other antiretrovirals.

Trials also showed that MPC-4326 had fewer of the drug-drug interactions that are common amongst some of the currently available HIV therapies.

For more information, please see the press release on the Myriad Pharmaceuticals website. For information on the terminated clinical trial, please see the United States clinical trials registry.

The guidelines include updates on preferred regimens for prevention of HIV transmission during pregnancy.

According to the report, fewer than 200 children are now born with HIV in the United States each year, as a result of efforts to limit mother-to-child transmission.

Transmission of HIV from a pregnant woman to her baby can occur during pregnancy, labor, or while breastfeeding after the baby is born. To prevent this, women are usually treated with antiretrovirals throughout the pregnancy and are told not to breastfeed their babies.

In this latest report, the NIH now recommends that pregnant women with HIV who are not already taking antiretrovirals start taking them sooner than previously suggested. The NIH suggests initiating treatment after the first trimester, and no later than 28 weeks into the pregnancy.

The guidelines also recommend pregnant women take a combination regimen consisting of at least three drugs, preferably two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor.

The recommended NRTI regimen is Combivir (zidovudine/lamivudine), based on clinical trials demonstrating its effectiveness.

The recommended NNRTI is Viramune (nevirapine), although only in women with CD4 cell counts of less than 250 cells/mm3 unless the benefits outweigh the risk of potential liver toxicity. Women already taking Viramune may continue during pregnancy.

The recommended protease inhibitor regimen is Kaletra (lopinavir/ritonavir). Alternative protease inhibitors include Norvir (ritonavir) in combination with Invirase (saquinavir), Crixivan (indinavir) or Reyataz (atazanavir).

Several treatments are not recommended for part or all of the pregnancy:

• The combination of stavudine (Zerit) and didanosine (Videx) are not recommended since they may cause serious side effects, including liver failure, in pregnant women.

• Sustiva (efavirenz) should not be taken in the first trimester of pregnancy because of possible harm to the baby. Sustiva is also an ingredient in Atripla (efavirenz/emtricitabine/tenofovir).

• Viread (tenofovir) should only be used when there is intolerance or resistance to zidovudine (Retrovir) or if the pregnant woman has hepatitis B because it may harm the baby. Viread is also an ingredient in Atripla and Truvada (emtricitabine/tenofovir).

• There is not yet enough data on Intelence (etravirine), Prezista (darunavir), Lexiva (fosamprenavir), Aptivus (tipranavir), Fuzeon (enfuvirtide), Selzentry (maraviroc), or Isentress (raltegravir) to recommend their use in pregnancy, although in some cases they may be used if other drugs are not well tolerated.

Prevention of mother-to-child transmission in HIV-positive women with hepatitis B (HBV) is also discussed. Treatment options depend on whether the mother requires anti-HIV treatment for her own health, anti-HBV treatment, or both.

The NIH also reaffirmed its recommendation that HIV-positive women should avoid breastfeeding. Although clinical trials in Africa have shown that antiretrovirals reduce the chances of transmitting HIV through breastfeeding, there is still a risk.

Since women in the U.S. have a safe, viable alternative to breastfeeding – formula feeding – the NIH strongly discourages HIV-positive women from breastfeeding.

After the baby is born, antiretroviral treatment of the infant is usually continued to ensure infection does not occur. The recommended treatment is zidovudine for six weeks after birth. In the new guidelines, the NIH warns that combining zidovudine with other treatments is not well-studied and should be done with caution.

Both Norvir and Kaletra have been associated with heart block, a problem with the heart’s electrical system, in babies, and therefore require especially close monitoring if used in infants.

Finally, food pre-chewed by HIV-positive caregivers should not be given to infants since this potentially increases the risk of HIV transmission.

The NIH welcomes feedback on the guideline revisions. Comments should be sent to ContactUs@aidsinfo.nih.gov with the subject line “Perinatal Comments” by June 7, 2010.

For more information, please see the complete guidelines at the NIH (pdf) website.

For HIV, scientists are increasingly realizing that an activated immune system is not necessarily a good thing. In fact, it seems to be a key to viral replication and disease progression.

“Disease associated with chronic infections such as HIV may not be so much a result of the virus attacking the host,” wrote researchers in an article released today in Science Translational Medicine, “but rather may be a result of the host’s immune system attacking the virus.”

Scientists have suspected for some time that uncontrolled inflammation is important for HIV replication early in infection. Recent studies, including this one, are providing even more evidence for this hypothesis.

In the study released today, scientists found that an enzyme called IDO1 may be a key part of creating an imbalance between two types of white blood cells in people with HIV.

The researchers believe the enzyme, IDO1, gets activated during the initial acute stage of HIV infection. The immune system usually uses IDO1 to help control infections.

However, IDO1 also appears to kill a particular type of CD4 white blood cell, called TH17, while increasing the amount of a different CD4 white blood cell, Treg.

The changing ratio between the two cell types is linked to faster disease progression in people with HIV. In this study, researchers confirmed that people with faster HIV progression have higher levels of the IDO1 enzyme than nonprogressors.

In essence, the stronger initial immune response, including IDO1 activation, led to further deterioration of the immune system later on.

The authors of the study are hopeful that their results could help doctors determine who might be at risk for rapid HIV progression, so they could start treatment for HIV infection earlier.

“We found that high levels of IDO1 activity predicted faster rates of progression,” said Dr. Joseph McCune, a lead author on the paper, in email correspondence with the Beacon.

“With further validation in larger groups of patients, our findings may later be translated to a clinical test that could help physicians to determine which patients are at risk for such rapid disease progression and which ones are not.”

Additionally, Phase 1 and Phase 2 clinical trials are already underway for drugs that inhibit the activity of IDO1 in cancer patients, and Dr. McCune’s group is planning to test these drugs in primates to see if they help with HIV infection.

Inhibition of the enzyme might be useful in slowing down disease progression, especially in conjunction with antiretroviral therapy.

“If heightened levels of IDO1 activity in fact drive the…cycle of disease progression, then inhibition of IDO1 activity should stop the cycle and provide benefit to the patient,” said Dr. McCune.

“Such inhibition may be particularly beneficial to those who are placed on effective antiretroviral therapy but who, because of continued inflammation, do not experience full immune recovery.”

If the results in primates are promising, Dr. McCune said, “It may make sense to move on to humans.”

Dr. McCune also suggested that it may be helpful to design a vaccine that can specifically increase the amount of TH17 cells, which are decreased by the IDO enzyme.

The results are still preliminary and need further confirmation, but Dr. McCune is optimistic. “Like all research, this study represents an incremental step; in this case, along the way to better understanding of HIV disease.”

“With better understanding, we will hopefully have better ways to treat and to prevent the disease in the future.”

For more information, please see the study in Science Translational Medicine (abstract).

The result has been budget shortfalls and a series of cutbacks in state ADAP programs around the country.

ADAPs are programs that provide antiretroviral drugs to low-income Americans living with HIV.

Although run by states, the majority of ADAP funding usually comes from the federal government through the Ryan White Program. State contributions typically account for 15 percent to 20 percent of ADAP budgets.

This year, many states are struggling to keep up with increased need for financial assistance from people living with HIV.

“The nation’s current economic situation, increased HIV testing efforts, and more individuals living longer have resulted in a ‘perfect storm’ that has rapidly resulted in swelling ADAP rolls,” wrote NASTAD in a press release.

In a report released May 4, NASTAD noted that ADAP budgets for 2009 increased 4 percent over the 2008 financial year with 63 percent of ADAPs experiencing a growth in budget. However, in many cases this was offset by increases in the number of people relying on ADAPs for their medications.

Furthermore, federal and state contributions to ADAP budgets are at or near all-time lows as a percent of the total budget. Rebate payments from pharmaceutical companies made up 31 percent of ADAP budgets in 2009.

“Increased funds from federal and state governments in addition to price freezes and increased discounts and rebates from companies are all necessary to sustain ADAPs until health reform is fully implemented in 2014,” wrote NASTAD.

During 2009, ADAPs added an average of nearly 1,300 people to its programs per month, an 80 percent increase over 2008. Seventy-five percent of individuals using ADAPs make less than 200 percent of the federal poverty level, or $22,000 per year.

ADAPs with reduced budgets are seeking to control costs by limiting the list of prescription drugs covered, instituting enrollment caps on particular medications, and restricting the number of prescriptions provided per month.

In addition, NASTAD reported last week that ten states had waiting lists, with over 1,000 people nationwide waiting for ADAP assistance.

ADAPs have been working with drug company patient assistance programs to help make medications as accessible as possible for those on the waiting lists.

In response to the crisis and lobbying efforts by NASTAD, the AIDS Healthcare Foundation (AHF), and other AIDS groups, several pharmaceutical companies have agreed to implement price freezes and other measures on drugs purchased through ADAPs.

Merck announced that it would extend price freezes on Isentress (raltegravir) and Crixivan (indinavir) through 2013 for ADAPs, increase discounts, and process rebate payments more quickly.

NASTAD also announced agreements with Abbott Laboratories and Tibotec Therapeutics to extend existing financial agreements. Abbott is the maker of Kaletra (lopinavir/ritonavir) and Norvir (ritonavir); Tibotec makes Prezista (darunavir) and Intelence (etravirine).

Nonetheless, state ADAP programs are pressing for additional federal funding to cover budget gaps.

“Many [ADAPs] are currently advocating for an emergency supplemental appropriation of $126 million to help sustain current services and eliminate waiting lists and other cost containment measures,” wrote NASTAD in a March “Crisis Strategy” briefing.

“Abbott, Merck, and Tibotec’s willingness to help with this crisis demonstrates that they are fully carrying their share of the burden, strengthening the case for further assistance from the federal and state governments at this critical time of unprecedented need for ADAPS,” added Jennifer Brown, spokesperson for the ADAP Crisis Task Force in a press release.

For more information, including the 2010 National ADAP Monitoring Project Annual Report (pdf), please see the NASTAD website.

Alcohol also increased viral load in patients taking antiretroviral therapy (ART) by promoting poorer adherence to ART. No significant increase in viral load was observed in patients not on ART.

The study was conducted over 30 months and followed HIV-positive adults with histories of alcohol and illegal drug use.

Most of the participants (77 percent) were African-American, with the remainder mostly Hispanic (13 percent) or Caucasian (7 percent).

Researchers monitored ART adherence, CD4 cell count, and HIV viral load (the amount of virus in the blood) in study participants to determine level of disease progression over time.

“These results provide evidence that frequent alcohol use alone, or in combination with crack-cocaine, is a risk factor for accelerated HIV disease progression,” wrote the study authors, “specifically a faster decline of CD4+ cell count and increased HIV viral load.”

The study found that alcohol users who consumed more than two drinks daily were almost three times more likely to develop a significant drop in CD4 cells. The drop occurred regardless of initial CD4 cell count and viral load, antiretroviral use over time, time since diagnosis, age, or gender.

They also found that the decline in CD4 cells from alcohol or substance abuse was independent of ART adherence.

The authors suggest that alcohol may directly influence disease progression by affecting CD4 cells and the immune system. This is consistent with previous studies showing that alcohol is an immune suppressant.

However, they acknowledged that other unmeasured behaviors might have accelerated HIV disease progression.

The study did not find a link between moderate alcohol intake (one or fewer drinks daily) and reduced CD4 cell count or increased viral load.

However, an earlier study showed significantly lower CD4 cell count and increased viral load in moderate and at-risk drinkers compared to non-drinkers. Researchers noted that these disparities require further investigation.

The effects of alcohol on HIV disease progression have been unclear, with many studies giving conflicting results.

Earlier observational studies, where HIV-positive individuals were followed over time, failed to establish a link between alcohol consumption and HIV disease progression.

Animal and laboratory studies, in contrast, have shown a significant effect of alcohol on HIV disease progression, susceptibility to AIDS-associated infections, and viral load. Studies conducted after the introduction of ART have also confirmed that alcohol reduces viral load response, CD4 cell recovery, and adherence to ART.

Additionally, a large study following heavy alcohol users consuming four or more times per week while receiving HAART concluded that heavy drinkers were less likely than moderate or non-drinkers to reach undetectable viral loads and were more likely to have low CD4 cell counts.

Experts advise that people with HIV should avoid recreational drugs and excessive drinking to minimize damage to the immune system.

For more information on alcohol and HIV, please see the United States Department of Veteran Affairs website. For more information on the study, please see the AIDS Research and Human Retroviruses (pdf) website.

Protease inhibitors are a class of antiretroviral drugs that prevent HIV from replicating by blocking a necessary protein called protease.

Drugs in this class include Aptivus (tipranavir), Crixivan (indinavir), Invirase (saquinavir mesylate), Kaletra (lopinavir/ritonavir), Lexiva (fosamprenavir), Norvir (ritonavir), Prezista (darunavir), Reyataz (atazanavir), and Viracept (nelfinavir).

Although some of the drug interactions had been known for specific protease inhibitors, the added information will affect all currently approved drugs in this class.

Drugs that should be avoided by individuals taking protease inhibitors include:

• Revatio (sildenafil), used to treat pulmonary arterial hypertension, a condition in which blood pressure in the arteries of the lungs is abnormally high. Protease inhibitors tend to increase concentrations of Revatio in the bloodstream, which could cause a dangerously low drop in blood pressure.
• Uroxatral (alfuzosin), which is used to treat men who have an enlarged prostate. Protease inhibitors increase the risk of severe low blood pressure in men taking Uroxatral.

The active ingredient in Revatio, sildenafil, is also the active ingredient in Viagra. Pfizer, which makes Viagra, recommends that men taking protease inhibitors should take no more than 25 mg of Viagra in a 48-hour period.

The FDA also listed several drugs that should not be given at the same time as protease inhibitors, including:

• Salmeterol (Serevent), which is used in asthma treatment. Protease inhibitors can lead to an increased risk of heart problems when given with salmeterol.
• Tracleer (bosentan), another drug for treatment of pulmonary arterial hypertension. Tracleer should not be given with Reyataz unless Norvir is also prescribed. Cotreatment with Tracleer and Reyataz without Norvir may result in higher blood concentrations of Tracleer, increasing both its activity and side effects.
• Colchicine, a natural product often used to treat gout, and which should not be given at the same time as protease inhibitors in patients with liver or kidney problems. Protease inhibitors may slow the rate at which the intestine and liver process colchicine.

Finally, several drugs were found to need dosing adjustments if administered with protease inhibitors. These include:

• Adcirca (tadalafil), another treatment for pulmonary arterial hypertension. Protease inhibitors can affect the amount of Adcirca in the body, so dosages should be monitored carefully.
• Colchicine for all patients taking protease inhibitors, when prescribed for the treatment of familial Mediterranean fever and gout or gout prevention.

Patients taking protease inhibitors should speak to their physicians before beginning or ending any drug regimens, and should tell doctors about all medications they are taking.

For more information on protease inhibitor drug-drug interactions, please see the FDA website.

Kaletra belongs to a class of anti-HIV drugs known as protease inhibitors. It is used in combination therapy to reduce the amount of HIV in the blood and to increase the number of CD4 cells in the body.

Once-daily dosing of Kaletra was already indicated for adult HIV patients new to ART. However, it had not yet been approved for treatment-experienced patients.

Abbott hopes the new dosing regimen will be simpler and more convenient.

“Adherence to treatment is critical to the effective management of HIV,” said Dr. Joseph Gathe, clinical instructor in the Department of Internal Medicine at Baylor College of Medicine, in an Abbott press release. “A Kaletra once-daily regimen can simplify HIV treatment and offers greater flexibility for patients.”

Approval for once-daily dosing was supported by a Phase 3 clinical trial conducted over 48 weeks in almost 600 treatment-experienced adults with HIV. It compared once-daily and twice-daily dosing of Kaletra in combination with other antiretrovirals.

The trial indicated similar effectiveness, safety, and tolerability, as well as a similar rate of HIV resistance development between once-daily and twice-daily Kaletra regimens.

Abbott warns that once-daily treatment should only be used in adult patients with minimal HIV resistance to protease inhibitors. The company also notes that Kaletra should not be given once-daily in combination with carbamazepine (Tegretol or Epitol), phenobarbital (Luminol), or phenytoin (Dilantin).

For more information, please see the press release on Abbott’s website.

The memorandum advised the Department of Health and Human Services (HHS) to initiate appropriate rules guaranteeing that Medicaid and Medicare-affiliated hospitals respect HIV/AIDS patients’ privileges to designate visitors.

It also stressed that hospitals participating in Medicaid and Medicare adhere fully to regulations designed to honor all patient’s advance directives, which include stipulations such as who should make health care decisions if the patient is unable to do so.

Obama emphasized that visitation privileges must not be contingent on race, nationality, religion, gender, gender identity, sexual orientation, or disability. This would prevent hospitals from denying visitation privileges to gay or lesbian partners.

Denied visitation has been a major issue in the HIV/AIDS community where the disease causes frequent illnesses and hospitalizations in many gay men.

The President acknowledged that under the current system, gay and lesbian Americans are uniquely affected by relatives-only policies at hospitals and are forbidden to act as legal proxies if their partners are incapacitated.

The Human Rights Campaign, the nation’s largest gay rights group, began working with the Obama administration to amend visitation rights following the case of an Olympia, Washington lesbian couple.

This couple was kept apart as one died from an aneurysm while hospitalized in Miami, Florida.

The new rules could also help widows and widowers who rely on friends and members of religious orders who care for one another.

The memorandum recommends that the HHS issue new guidelines and provide technical assistance to participating Medicaid and Medicare hospitals to aid regulatory compliance and allow appropriate measures for fully enforcing the regulations.

Obama asked HHS to recommend appropriate actions that address hospital visitation, medical decision making, and other health care issues, particularly those that affect LGBT patients and families, within the next six months.

Recently, North Carolina adapted its Patients’ Bill of Rights to allow patients the right to designate visitors who will receive the same rights as immediate family members, regardless of whether they are legally related to the patient or not.

Delaware, Nebraska, and Minnesota have also implemented similar laws.

For more information, please visit the White House website.

Mylan Gets Approval For Generic Version Of Videx EC HIV Treatment – Early last week, Mylan Inc. announced that it had received approval from the United States Food and Drug Agency for its generic version of Videx EC (didanosine). Videx EC, manufactured by Bristol-Myers Squibbs, is an anti-HIV drug that stalls replication of the HIV virus when taken in combination with at least two other drugs. Approval was obtained under the President’s Emergency Plan for AIDS Relief. Mylan Pharmaceuticals plans to start marketing the drug in the U.S. in the current quarter. For more information, please see the Mylan website.

Fall And Spring Cruises For HIV-Positive Gay Men – Carnival Cruise lines will run cruises from May 2 to May 9 and October 23 to October 31 for gay HIV-positive men. The cruises, which travel throughout the Caribbean and Mexico, include social events, games, informative lectures, spiritual workshops, and Q&A sessions with HIV experts. Participants may go on both cruises, and eligibility is unaffected by age, disease stage, or previous experience on a cruise ship. A portion of the proceeds are donated to HIV organizations and charities. For more information, please see the Gay Men’s HIV Retreat website.

For a more detailed listing of HIV/AIDS related events, please check the AIDS Beacon Events Calendar.

ONAP Releases Community Recommendations Report For National HIV/AIDS Strategy – The Office of National AIDS Policy recently released a report of major HIV/AIDS policy recommendations following feedback from the HIV-positive community in the United States. Recommendations include increased HIV prevention and education for high-risk groups, an extension of support services for people living with HIV/AIDS, and effective coordination and evaluation of HIV prevention and treatment activities across the Federal government. The report also noted that the stigma associated with HIV diagnosis often prevents testing and enrollment in care. The recommendations will be used by federal, state, and local agencies as a resource and planning tool. For more information, please see the ONAP website.

Workshop On How To Discuss Your HIV Status With Others – Positive Impact is running a five day workshop that teaches African-American gay men skills for discussing HIV status with family, friends, and sexual partners. “Brutha, Can We Talk: A Healthy Relationships Program” is a 5-session workshop that will be held 1 p.m. to 3 p.m. on April 26 through April 30 in Atlanta, GA. For more information, please see the Positive Impact website.

For a more detailed listing of HIV/AIDS related events, please check the AIDS Beacon Events Calendar.

Sustiva, which is an antiretroviral drug made by Bristol-Myers Squibb, is approved by the FDA for use in combination with other antiretroviral agents in HIV-positive adults and children older than three years of age.

Sustiva is classified as a Pregnancy Category D drug, indicating there is evidence it can cause birth defects.

The new label has updated information on fetal harm, including neural tube defects (birth defects of the brain and spinal cord), that can occur if Sustiva is taken during the first trimester of pregnancy.

The Antiretroviral Pregnancy Registry, which monitors fetal outcomes of pregnant women exposed to Sustiva, reported birth defects in about three percent of live births involving first-trimester exposure to Sustiva, and in just over 3.5 percent of live births involving second/third-trimester exposure.

Additionally, the revised label warns of potential liver toxicity in people taking Sustiva.

Although most cases of serious liver problems occurred in patients with pre-existing liver dysfunction, a few cases occurred in patients without any pre-existing liver disease.

The liver problems encountered sometimes culminated in transplantation or death.

As a result, the FDA recommends considering liver enzyme monitoring in Sustiva patients, regardless of whether they have pre-existing liver dysfunction or not.

The label also cautions that Noxafil (posaconazole), which is used to treat Candida and other yeast infections, only be taken in combination with Sustiva if the benefit of the treatment offsets the risks. Sustiva can reduce the amount of Noxafil in the blood, making it less effective for treating infections.

Finally, the FDA warns that if Sustiva is taken with Selzentry (maraviroc), changes in the dose of one of the drugs may be necessary.

For more information, please see the FDA Web site.

In its letter to BMS, AHF urged that AIDS Drug Assistance Programs (ADAPs) nationwide should receive the drug at a price similar to prices of first-line antiretroviral drugs like Viread (tenofovir) and Sustiva (efavirenz).

ADAPs throughout the United States aim to provide AIDS drugs like Reyataz to low-income people in need. This aim, however, is becoming increasingly difficult to meet as drug prices continue to rise.

Since 2003, BMS raised the price of Reyataz by 25 percent. The average wholesale price to pharmacies is now over $13,000 per year per patient, making it one of the most expensive first-line antiretroviral drugs on the market.

Even though ADAPs typically receive drugs at lower costs than pharmacies, AHF claims that the high cost of Reyataz, which must be taken along with at least two other HIV/AIDS drugs, strains ADAPs.

Across the country, states have been forced to reduce ADAP services and enrollment due to the high price of AIDS drugs like Reyataz.

Although BMS offers financial assistance through a co-payment program and the Access Virology Patient Assistance Program for those who cannot afford Reyataz, AHF claims that these efforts are undermined by the high price BMS charges for the drug.

But AHF acknowledges that Reyataz is not the only expensive AIDS drug.

In September 2009, after Isentress (raltegravir) received approval as a first-line AIDS treatment, AHF criticized Merck for Isentress being the most expensive first-line AIDS treatment.

In October 2009, after the FDA advisory committee advocated for approval of Pfizer’s Selzentry (maraviroc) as a first-line therapy, AHF urged Pfizer officials to reconsider the pricing of their drug.

AHF insists that the high cost of other HIV/AIDS drugs is no excuse for BMS to push up the price of Reyataz and that all AIDS drug manufacturers must establish reasonable pricing and access policies so that ADAP can continue to provide treatment to the people who need it.

For more information, please read the AHF press release and previous Beacon coverage of AHF’s campaign to lower drug prices.

However, IL-2 therapy was associated with a higher rate of opportunistic infections, which take advantage of weaknesses in the immune system, and death compared to no treatment. The study was published in the journal PLoS One.

The addition of short courses of antiretroviral therapy (ART) to the IL-2 treatment did not further increase the number of CD4 cells compared to IL-2 alone.

ART, a combination of at least three antiviral drugs, is designed to suppress and stop the progression of HIV infection. However, it does not completely eradicate the HIV virus, and once started, the treatment must be continued for life, since interruptions or discontinuation can increase risk of disease progression or death.

The purpose of the study, known as STALWART, was to investigate whether IL-2 alone or in combination with short courses of ART would enhance immunologic response without the adverse effects of continuous ART.

The study evaluated the safety and efficacy of IL-2 in 267 patients not yet ready for continuous ART.

Participants received either no treatment, IL-2 for five consecutive days every eight weeks for three cycles, or the same IL-2 regimen with the addition of ten days of ART administered around each IL-2 cycle.

At week 32 of the study, the mean change in CD4 cells in participants not receiving treatment was -22 cells/mm³ compared to a change of +114 for IL-2 recipients. Participants receiving IL-2 plus ART showed a similar increase in CD4 cells to those receiving IL-2 alone.

Increased CD4 counts in IL-2 patients delayed the start of continuous ART. However, the amount of HIV virus in the blood stream was unaffected by treatment with IL-2.

Despite the potential benefits of IL-2, treatment with the drug was associated with increased side effects, opportunistic infections, and progression to AIDS or death, which calls into question the potential of IL-2-induced CD4 cells to fight disease.

Patients receiving IL-2 were more than twice as likely to develop moderate or severe side effects as patients receiving no therapy, and those receiving ART in addition to IL-2 were more than four times as likely. Common side effects included fever, nausea, muscle pain, and rash.

Overall, researchers believe that IL-2 might be an effective strategy to complement ART, rather than to replace it.

They also concluded that CD4 counts might not be the best way of measuring immune function in IL-2 recipients, since the efficacy of IL-2 induced CD4 cells is uncertain. Instead, researchers suggest it might be useful to differentiate IL-2 induced cells to more accurately measure disease progression in patients who have received IL-2.

To extend safety evaluations, participants in the study will be offered an additional two years of clinical follow-up.

Two other studies (ESPRIT and SILCAAT), designed to evaluate the clinical efficacy of intermittent IL-2 plus continuous ART compared to ART alone, also concluded that the addition of IL-2 did not slow disease progression or prevent death compared to ART alone, despite increased CD4 cells.

Another clinical trial (ANRS 119) compared IL-2 therapy alone to no intervention and found that IL-2 recipients delayed ART initiation compared to controls and did not experience increased clinical events.

“We currently have no plans to carry out new studies with IL-2. However, other [signaling molecules] like IL-7, which are better tolerated, might be more interesting to assess,” said Jean-Michel Molina, principle investigator of the ANRS 119 study.

For more information regarding the STALWART study, please see the article in PLoS One.