Based on their results, the study authors recommended future studies to look for links between individual protease inhibitors and increased risk of death. However, they also noted that deaths are rare, which makes it difficult to find such links even if they exist.

According to the study authors, concerns have arisen recently that protease inhibitors may be linked to problems with the electrical conductivity of the heart. In particular, researchers have found that the drugs may affect heart rate and the timing of heartbeats.

The researchers noted that these heartbeat abnormalities, which can be measured on an electrocardiogram, are associated with congestive heart failure and risk of sudden death.

In this study, the authors evaluated whether people with HIV who are taking protease inhibitors are at increased risk for non-hemorrhagic stroke, a type of stroke caused by lack of oxygen in the brain rather than bleeding, or sudden death. Non-hemorrhagic strokes are a common complication of heart attacks.

The study included 49,737 HIV-positive adults, 64 percent of whom were exposed to protease inhibitors for a median of 1.5 years. The median participant age was 43 years old. About half were Caucasian, and 73 percent were male.

Results showed that less than 0.2 percent of participants suffered from sudden death during the study and about 0.3 percent suffered a non-hemorrhagic stroke.

Participants who experienced either sudden death or a stroke were more likely to be male, have a low body mass index (less than 18 kg/m²), smoke, take medications for high blood pressure, or have diabetes.

In addition, participants who suffered sudden death or a stroke had a longer median exposure to protease inhibitors, nucleoside reverse-transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors. They also had higher cholesterol and triglyceride levels and lower CD4 (white blood cell) counts.

After adjusting for other risk factors such as age and smoking, the researchers found that current protease inhibitor use was not associated with an increased risk of either outcome. However, cumulative protease inhibitor use was associated with a slightly higher risk of sudden death and stroke.

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

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).

Gilead Receives Approval For Eviplera In Europe – The European Medicines Agency (EMA) has approved Gilead Sciences’ new once-daily combination antiretroviral pill Eviplera (rilpivirine/emtricitabine/tenofovir) for the treatment of HIV in previously untreated adults with viral loads (amount of HIV in the blood) of 100,000 copies per milliliter or less. The approval means that Eviplera can be marketed in all 27 countries in the European Union. Eviplera, known as Complera in the U.S., was approved by the U.S. Food and Drug Administration in August. For more information, please see the Gilead Sciences press release.

AIDS Deaths Continue To Drop Worldwide – An annual report from the United Nations shows that the number of deaths worldwide due to AIDS has continued to drop for the third year in a row. The number of new HIV infections also fell 21 percent in 2010 compared to 1997; 70 percent of new infections were in sub-Saharan Africa. However, the number of people on antiretrovirals increased 20 percent in 2010 in sub-Saharan Africa, bringing the total to 50 percent of clinically eligible people with HIV in low- and middle-income countries. The report also notes that due to longer lifespans and greater survival rates, the number of people living with HIV now stands at an estimated 34 million, the highest ever. For more information, please see the United Nations report (pdf) or the article in the Washington Post.

Study Finds Viread Vaginal Gel Is Safe But Ineffective For HIV Prevention – Results from the Oral Interventions to Control the Epidemic (VOICE) study indicate that a vaginal gel containing 1 percent Viread (tenofovir) is safe but ineffective at preventing HIV infection in women. Based on the results, the National Institutes of Health, which is funding the study, has decided to drop the vaginal gel from the study. The trial, whose purpose is to provide women with methods to prevent HIV infection, will continue to evaluate the safety and efficacy of Truvada (emtricitabine/tenofovir) pills instead. The VOICE study was first modified in September after results showed that a Viread pill was also ineffective (see related AIDS Beacon news). For more information, please see the National Institutes of Health press release.

“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 said that a comparison of their results with studies of HIV-negative, older adults suggests that people with HIV have around a three- to four-fold higher risk for cancer and heart attacks and a five-fold higher risk for diabetes than people of the same age without HIV.

Based on their results, the authors recommended that older adults with HIV be screened for additional illnesses and try to minimize risk factors for these diseases, such as being overweight.

With the advent of highly active antiretroviral therapy (HAART), many people with HIV are living well into older age; a recent study found that life expectancy for people with HIV is now close to that of people without HIV (see related AIDS Beacon news). In addition, the rate of new HIV infections in older adults continues to rise.

As people with HIV age, however, they become more prone to many of the same age-related illnesses as people without HIV, including cancer, heart disease, and diabetes.

According to the study authors, previous studies have looked at the rates of individual diseases, such as diabetes, in aging people with HIV; however, few studies have looked at the rates of age-related diseases overall in this population.

In this study, the researchers aimed to determine the rates of such age-related diseases in people with HIV aged 50 and above compared to younger adults with HIV.

The study included 8,444 HIV-positive adults aged 16 years or older, with a median age of 45 years old. Most participants (71 percent) were male. The median age at HIV diagnosis was 29 years old, and the median length of HIV infection was 15.4 years.

The researchers categorized participants into three age groups: younger than 50 (68 percent of participants), 50 to 64 years old (26 percent), and 65 or older (5 percent).

Results showed that participants older than age 50 were more likely to have other illnesses and to die than participants younger than 50. In particular, older participants were at a higher risk for bacterial pneumonia, stroke, blocked coronary (heart) arteries, heart attack, bone fractures, osteoporosis, diabetes, inflammation of the pancreas, and non-AIDS-defining cancers.

The risks remained higher in older participants after adjusting for CD4 (white blood cell) counts, viral loads (amount of HIV in the blood), sex, current or former smoking, current or former injection drug use, and length of HIV infection.

However, older study participants were not at a higher risk of HIV-related illnesses.

Results also showed that female participants had about a three-fold higher risk of osteoporosis than male participants.

In addition, former injection drug users were at a higher risk of bacterial pneumonia, liver problems, and death; current injection drug users were at a higher risk of liver problems and death. Former smokers were at a higher risk of death; current smokers were at a higher risk of bacterial pneumonia and death.

Higher CD4 counts were linked to a slightly lower risk of bacterial pneumonia, bone fractures due to bone fragility, osteoporosis, new AIDS-defining illnesses, and death. Higher viral loads were associated with an increased risk of HIV-related illnesses.

Study participants with longer HIV infections were slightly less likely to develop HIV-related illnesses.

During the course of the study, 2 percent of participants died. The leading causes of death were cancer (23 percent), infectious diseases (15 percent), and heart-related diseases (12 percent).

A comparison with other European studies on illnesses in aging HIV-negative adults suggested that people with HIV were about 4 times more likely to get cancer, 3.5 times more likely to have a heart attack, and over 5 times more likely to have diabetes than people of the same age without HIV.

However, the study authors noted that these are just estimates, since their study did not include a matched HIV-negative study population for a true comparison.

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

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 study authors suggested that various factors, including better drugs, earlier detection, and increased experience of physicians in treating HIV, may have contributed to the rise in life expectancy.

The authors also suggested that the link between low pre-treatment CD4 (white blood cell) counts and shorter life expectancy may serve as a useful guide for HIV-positive people who are deciding when to start antiretroviral therapy.

However, the authors pointed out that a number of study participants were immigrants from Sub-Saharan Africa. This demographic difference may influence the relevance of the results to people with HIV in the United States.

Life expectancy at a given age is the expected number of years of life remaining. In the general population, several factors, including sex, race, and lifestyle habits, are known to affect life expectancy.

Although previous studies have examined mortality rates in HIV-positive people, estimates of how long people with HIV are likely to live have remained imprecise.

In their study, researchers at the University of Bristol sought to estimate how life expectancy for people starting antiretroviral therapy has changed over time. They also attempted to determine how life expectancy was affected by how early or late people initiated therapy.

The researchers analyzed data from 17,661 participants who started antiretroviral therapy in clinics across the U.K. from 1996 to 2008. All participants were over 20 years of age, 75 percent were men, and 58 percent were white.  All participants had CD4 counts of 350 cells per microliter or less when they started treatment.

The researchers collected data in four time intervals starting from 1996 to 1999 and ending with 2006 to 2008 to estimate how life expectancy at age 20 changed over time. They then compared these values to the life expectancy at age 20 of the general population. The researchers also determined whether life expectancy in people with HIV depended on factors such as sex and pre-treatment CD4 counts.

Results showed that persons starting antiretroviral therapy in 2006 to 2008 could expect to live nearly 46 years after the age of 20, while their counterparts who started treatment in 1996 to 1998 could expect to live for 30 years after the age of 20.

Results also showed that the life expectancy for HIV-positive people at age 20 is still lower than that of the general population by about 13 years. In addition, while in the general population women could expect to outlive men by nearly four years, in the HIV-positive population women could expect to outlive men by almost 11 years. The researchers suggested that this could be because women are screened for HIV during pregnancy and are therefore diagnosed earlier, or because of lifestyle differences such as alcohol and drug use.

Participants whose pre-treatment CD4 counts were less than 200 cells per microliter had a significantly lower life expectancy (38 to 41 years after age 20) than those with counts between 200 and 350 cells per microliter (53 years after age 20).

A total of 7 percent of participants died during the course of the study.

For further information, please see the related article in the British Medical Journal.

“The positive trends we reported between 2000 and 2009 in this study probably result from improvements in tolerability and ease of use of drug regimens, and in the availability of drugs with non-overlapping resistance profiles,” wrote the study authors.

“Our results are consistent with recent studies indicating that the proportion of overall clinic populations with suppressed viral load has increased with time,” they added.

However, the study authors also noted that the development of new drugs that work on drug-resistant HIV will continue to be necessary, since people starting antiretroviral therapy today will eventually develop HIV that is resistant to current newer antiretrovirals.

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.

According to the study authors, resistance to all three main classes of antiretrovirals – nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors – has become less common with the advent of combination antiretroviral therapy. However, the prognosis for patients who do develop triple-class drug resistance after combination therapy has not been well studied.

In this study, researchers examined the treatment outcomes, including development of AIDS and risk of death, over time for people with multi-drug resistant HIV. More specifically, they monitored individuals whose HIV was resistant to at least two different NRTIs, one NNRTI, and one protease inhibitor.

The study included 2,476 HIV-positive individuals aged 16 years or older who started antiretroviral therapy between 1998 and 2001. All participants had triple-class drug resistant HIV. The median participant age at the time of treatment failure due to drug resistance was 40 years old. A majority of participants (67 percent) were male.

Results showed that the rate of participants who successfully achieved undetectable viral loads after changing drug regimens due to treatment failure increased from 20 percent in 2000 to 58 percent in 2008. In addition, the researchers found that 49 percent of participants who experienced initial treatment failure in 2008 still had undetectable viral loads in 2009, compared to 17 percent of participants in 2001 who experienced initial treatment failure in 2000.

The researchers also found that men who have sex with men were more likely to respond to treatment than heterosexual men and women or injection drug users. In addition, participants with lower viral loads and higher CD4 (white blood cell) counts at the time of treatment failure were more likely to successfully achieve undetectable viral loads after changing regimens, as were participants who were monitored in later calendar years during the study.

Results also showed that there were half as many AIDS-defining illnesses among participants in 2008 to 2009 as in 2000 to 2002. The death rate also dropped by half, but the difference was not considered significant.

Injection drug users, participants younger than 30 or older than 50, and people who had an AIDS-defining illness were most likely to die during the study.

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

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).

However, the study authors did find a decreased risk of AIDS or death for people with HIV who initiated treatment at CD4 (white blood cell) counts of less than 500 cells per microliter.

Based on the results, the study authors said that patients and physicians should carefully weigh the benefits and drawbacks of starting treatment early.

“The drugs used to treat HIV are expensive, treatment is life-long, and the side effects can be serious. So we really need to know if the patient’s investment will pay off, how large the benefit is likely to be, and how long it will take to realize it,” said Prof. Michele Jonsson Funk, a research assistant professor at the University of North Carolina School of Medicine and one of the authors of the study.

“I think the most important finding (given what we have learned in recent years from other large, observational, clinical cohort studies) is that the jury is still out on the benefit of initiating therapy at CD4 [counts] greater than 500, at least in terms of the patient’s own HIV disease progression,” she added.

However, the study authors also noted that the study looked only at risk of AIDS and death, and that it is possible that starting treatment early could affect other outcomes such as risk of heart disease and neurological problems.

“If there was a substantial benefit in terms of reducing cardiovascular or cancer outcomes, that could certainly make a compelling case for earlier initiation,” said Prof. Jonsson Funk.

The question of when people with HIV should start antiretroviral therapy is still largely unresolved. Previous studies have shown a definite benefit in starting treatment at CD4 counts of 350 or below, and several studies have also shown that starting at a CD4 count threshold of 500 cells per microliter is beneficial (see related AIDS Beacon news). Based on these results, current U.S. treatment guidelines recommend starting therapy at a CD4 count of 500 or below.

However, there is a question of whether starting treatment even earlier, at CD4 counts above 500 cells per microliter, could lead to better health outcomes. For example, some studies have suggested that starting therapy as soon as a person is diagnosed as HIV positive and while CD4 counts are still high may result in better preservation of the immune system and potentially fewer HIV-related health problems over time (see related AIDS Beacon news).

On the other hand, starting treatment earlier is more expensive and leads to longer exposure to antiretroviral drugs and their side effects, which have been linked to health problems such as diabetes and heart disease. Earlier treatment initiation also means patients must adhere to an antiretroviral regimen for a longer period of time.

In this study, researchers evaluated the effects of starting treatment at CD4 counts of 800 cells per microliter and below to see if early treatment reduced participants’ risk of progressing to AIDS or dying.

The study included 9,455 HIV-positive patients aged 13 years old or older from Europe, Australia, and Canada. The median age at time of HIV diagnosis was 30 years old, and the median length of infection before starting the study was 1.3 years. All participants had CD4 counts of less than 800; none had previously taken antiretrovirals.

The researchers classified participants according to their CD4 counts: 0 to 49 cells per microliter, 50 to 199, 200 to 349, 350 to 499, and 500 to 799. They then monitored outcomes for participants who decided to initiate treatment during each month of the study compared to participants who decided to wait. The study was conducted from January 1996 to May 2009. Participants were followed for a median of five years.

Results showed that for participants with CD4 counts below 500, initiating antiretroviral therapy resulted in a lower risk of progressing to AIDS and fewer deaths than deferring treatment. For example, participants with CD4 counts between 350 and 499 cells per microliter who started treatment had a 25 percent lower risk of progressing to AIDS or dying than participants who chose not to start therapy.

For participants with the lowest CD4 counts, 0 to 49 cells per microliter, treatment initiation was associated with a 68 percent lower risk of AIDS or death.

However, the researchers found no effect for participants with CD4 counts of 500 cells per microliter or above.

The study authors also noted that although there was a benefit to starting treatment in participants with CD4 counts between 350 and 499 cells per microliter, this benefit was small and was not evident for up to two years after starting treatment. As a result, they suggested that people with HIV whose CD4 counts fall within this range consider the risks and benefits of antiretroviral therapy before starting treatment.

For more information, please see the study in the Archives of Internal Medicine (abstract) or the University of North Carolina School of Medicine press release.