Based on their results, the researchers recommended further research into treatment regimens that do not contain nucleoside reverse transcriptase inhibitors (NRTIs) – such as Truvada – which currently form the backbone of antiretroviral therapy. They also noted that longer trials with more participants would be needed to confirm the long-term safety and efficacy of non-NRTI-based regimens.

The results were presented last week at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2011).

Traditional combination antiretroviral therapy regimens consist of two NRTIs plus at least one additional anti-HIV drug from a different class. However, due to side effects associated with NRTIs and the fact that some patients cannot take them due to allergies or other conditions, researchers have begun exploring alternative “NRTI-sparing” regimens (see related AIDS Beacon news).

In this study, researchers examined the efficacy of the non-NRTI-based regimen of Kaletra (lopinavir/ritonavir) plus Selzentry (maraviroc) versus the more traditional regimen of Kaletra plus Truvada (emtricitabine/tenofovir). Truvada is a combination of two NRTIs, while Kaletra is a protease inhibitor and Selzentry is a CCR5 inhibitor, which is a relatively new type of antiretroviral.

The trial included 38 HIV-positive adults who had not previously been treated for HIV. Half the participants were randomly assigned to receive Kaletra plus Selzentry, and the other half were assigned to take Kaletra plus Truvada. The researchers then assessed participants’ CD4 (white blood cell) counts and viral loads (amount of HIV in the blood) at 4, 12, 24, 36, and 48 weeks after starting treatment.

Results showed that after 48 weeks, participants in the non-NRTI Kaletra plus Selzentry group had significantly higher increases in CD4 counts than participants in the Kaletra plus Truvada group. The average increase in CD4 count for the Kaletra/Selzentry group was 226 cells per microliter, compared to 125 cells per microliter in the Kaletra/Truvada group.

Additionally, most participants in the non-NRTI group (83 percent) achieved undetectable viral loads by week 12, compared to less than half of patients in the Truvada group. By 48 weeks, 95 percent of participants in the Kaletra/Selzentry group had undetectable viral loads, compared to 83 percent of participants in the Kaletra/Truvada group.

The researchers also noted that three participants taking Kaletra plus Truvada had to interrupt treatment due to diarrhea. Overall one person in the Kaletra/Truvada group discontinued treatment, compared to none in the Kaletra/Selzentry group.

For more information, please see the study abstract and presentation (pdf) on the IAS 2011 conference website.

NIH Expands Phase 4 Clinical Trial On Early HIV Treatment Initiation – The U.S. National Institutes of Health (NIH) announced last week that they have expanded the Strategic Timing of Antiretroviral Treatment (START) clinical trial and are currently recruiting participants. The START trial aims to determine the benefits and risks of starting therapy early, at CD4 (white blood cell) counts above 500 cells per microliter, as compared to waiting until counts drop to 350. The World Health Organization currently recommends starting treatment at a CD4 count of 350; U.S. guidelines recommend starting at 500. The NIH decided to expand the trial after a successful pilot study involving 1,000 participants. The expanded trial will include up to 4,000 participants worldwide. For more information, please see the NIH press release or the U.S. Clinical Trials Registry.

“Big Bang Theory” And “Pushing Daisies” Actors To Debut In Broadway AIDS Play “The Normal Heart” – Jim Parsons and Lee Pace, the Emmy award-winning stars of the television comedies “The Big Bang Theory” and “Pushing Daisies,” will be debuting in a new Broadway production of “The Normal Heart.” The play centers around HIV/AIDS activists in New York City in the early 1980s. The play will preview April 19 with an opening night of April 27. It will run for 12 weeks. Additional cast members include Ellen Barkin, John Benjamin Hickey, and Tony award-winner Joe Mantello. For more information, please see the New York Times article or “The Normal Heart” website.

Kidney disease is a common problem for people with HIV, particularly as they get older. Depending on how severe the kidney disease is, a variety of options are available, ranging from diet changes to a kidney transplant. Some choices, such as a kidney transplant, were once thought to be too risky, but are now increasingly available to people with HIV.

Growing rates of kidney disease and other chronic conditions are both good news and bad news for people with HIV. Highly active antiretroviral therapy (HAART) has been very effective in prolonging lifespans and decreasing mortality from HIV and other related diseases.

However, this also means that HIV-positive individuals are now more likely to die of chronic diseases, such as kidney disease.

“Organ failure is increasingly the cause of [death] in HIV-infected individuals, as improvements in antiretroviral therapy have led to longer life spans and much less death due to opportunistic disease,” said Dr. Jonah Odim, a medical officer in NIAID’s Division of Allergy, Immunology and Transplantation and Dr. Larry Fox, a medical officer in NIAID’s Division of AIDS, in correspondence with The AIDS Beacon.

Kidney disease is estimated to affect about 30 percent of people with HIV and cause more than 10 percent of HIV-related deaths.

What Is Kidney Disease?

The kidneys perform the necessary functions of regulating the body’s fluids and filtering the blood to eliminate waste products and toxic substances.

Kidney disease occurs when the kidneys lose the ability to perform these functions. As a result, water, waste, and toxins build up in the body. Chronic kidney disease is defined by evidence of kidney damage or decreased kidney function for at least three months.

There are five different stages of kidney disease, based on how well or poorly the kidneys are working. The fifth and final stage is referred to as end stage renal (kidney) failure (ESRF) or sometimes just kidney failure. When patients are in ESRF, their kidneys shut down and are almost completely unable to function properly.

Kidney disease can cause other health conditions such as heart disease, nerve damage, bone disease, and anemia (a decrease in red blood cells that prevents the body from getting enough oxygen).

People with HIV are at an increased risk of kidney disease because the virus interferes with the kidneys’ ability to function correctly. People with advanced HIV who have a low CD4 (white blood cell) count and a high viral load (amount of virus in the blood) are at greater risk for developing kidney disease. Older people with HIV are also at greater risk of kidney disease.

Symptoms

Some symptoms of kidney disease may include:

• Urinating pale urine more often than usual, darker urine less often, or urinating foamy, bubbly or bloody urine
• Difficulty urinating, or waking often at night to urinate
• Swelling in the legs, feet, ankles, face, and hands
• Excess fatigue
• Itching or rash
• Shortness of breath
• Lack of appetite or a metallic taste in the mouth
• Nausea and vomiting
• Fainting, dizziness, or difficulty concentrating
• Feeling excessively cold
• Leg, back, or side pain.

Causes

The two most common causes of kidney disease are high blood pressure (hypertension) and diabetes, a condition in which the body cannot properly manage its blood sugar levels.

Certain factors beyond a patient’s control, such as family history, premature birth, and trauma or injury may be factors in kidney disease. African-Americans and Hispanics are also at higher risk of kidney disease.

HIV itself can cause damage to the kidneys, called HIV-Associated Nephropathy. It is thought to be caused by the virus infecting and damaging cells in the kidneys. Kidney damage from HIV can occur even in people taking antiretroviral drugs.

Medications for HIV and HIV-related health problems are also harsh on the kidneys and may, over time, contribute to kidney disease.

Antiretroviral drugs that have been associated with kidney disease include Viread (tenofovir), Crixivan (indinavir), Reyataz (atazanavir), and possibly Kaletra (lopinavir/ritonavir). Selzentry (maraviroc) is not recommended for people with severe kidney disease or ESRF.

Other medical conditions that may increase the risk of kidney disease are hepatitis C infection; kidney stones, which cause the urinary tract to become blocked; glomerulonephritis, an inflammatory immune response to infections such as strep throat that can damage the kidneys; and allergic reactions to antibiotics such as penicillin and vancomycin.

The use of drugs such as heroin and cocaine and excessive use of painkillers containing ibuprofen (Advil, Motrin), naproxen (Aleve), aspirin, or acetaminophen (Tylenol) may also contribute to kidney disease.

Diagnosis

There are several tests used to determine if a person has kidney disease. The most common are blood and urine tests that measure kidney function.

Blood tests monitor blood pressure (which can increase in people with kidney disease) and the amount of a substance called creatinine in the blood. Creatinine is a waste product of metabolism and should be filtered from the blood by the kidneys.  High creatinine levels in the blood can indicate kidney dysfunction.

Urine tests monitor the levels of protein in the urine. When the kidneys are not functioning well, proteins start to build up in the urine, along with red and white blood cells. If high protein levels or blood cells are found in the urine, this also usually indicates kidney disease.

Additional tests might include an ultrasound, MRI, or CAT scan to image the kidneys. In some cases a kidney biopsy might be performed, in which a small piece of the kidney is taken and examined under a microscope.

According to the National Kidney Foundation, people with HIV who have any additional risk factors for kidney disease should be tested for kidney disease at least once a year.

For more information on treatment of kidney disease, please see Part 2 of this series. For more information on kidney transplants for people with HIV, please see Part 3 of this series.

La insuficiencia renal es un problema común para los individuos con VIH, especialmente a medida que envejecen. Dependiendo de la severidad de la insuficiencia renal, hay una variedad de opciones terapéuticas disponibles, que van desde cambios en la dieta hasta un trasplante de riñón. En el pasado se pensaba que alguna de las opciones, como el trasplante de riñón, eran demasiado peligrosas, pero hoy en día ha aumentado mucho su disponibilidad para la gente con VIH.

El aumento de la incidencia de las enfermedades renales y otras enfermedades crónicas supone a la vez buenas y malas noticias para las personas con VIH. La terapia antirretroviral de alta actividad (HAART, por sus siglas en inglés) ha prolongado de manera muy eficaz su expectativa de vida, disminuyendo la mortalidad por VIH y otras enfermedades relacionadas con el virus.

Sin embargo, esto también significa que hoy en día las personas con VIH son más propensas a morir de enfermedades crónicas, como la insuficiencia renal.

“Los fallos orgánicos son cada vez más a menudo la causa de [la muerte] en los individuos infectados por el VIH, puesto que las mejoras en la terapia antirretroviral han dado lugar a una mayor expectativa de vida y muchas menos muertes debidas a enfermedades oportunistas”, dijeron el Dr. Jonah Odim, médico militar de la División de alergias, inmunología y trasplantes del Instituto nacional de alergias y enfermedades infecciosas (NIAID, por sus siglas en inglés) y el Dr. Larry Fox, médico militar de la División de SIDA del NIAID, en correspondencia electrónica con The AIDS Beacon.

Se estima que las enfermedades renales afectan a alrededor del 30 por ciento de las personas con VIH y causan más del 10 por ciento de las muertes relacionadas con el VIH.

¿Qué es la insuficiencia renal?

Los riñones realizan la imprescindible tarea de regular los fluidos del cuerpo y filtrar la sangre para eliminar los residuos y sustancias tóxicas del organismo.

La insuficiencia renal se produce cuando los riñones pierden la capacidad de realizar estas funciones. Como resultado, el agua, los residuos y toxinas se acumulan en el cuerpo. La insuficiencia renal crónica se define por la evidencia de daño renal o la disminución de la función renal durante al menos tres meses.

La insuficiencia renal tiene cinco fases, clasificadas según el nivel de funcionamiento de los riñones. La quinta y última fase se conoce como insuficiencia renal (del riñón) en fase terminal (ESRF, por sus siglas en inglés) o, a veces, simplemente como insuficiencia renal. Cuando los pacientes están en ESRF, sus riñones se paralizan y dejan de funcionar correctamente.

La insuficiencia renal puede causar otros problemas de salud, como enfermedades del corazón, daño nervioso, enfermedades óseas y anemia (disminución del número de glóbulos rojos que impide que el cuerpo obtenga suficiente oxígeno).

Las personas con VIH corren un riesgo mayor de padecer insuficiencia renal, ya que el virus interfiere con la capacidad del riñón para funcionar correctamente. Las personas con VIH avanzado que tienen una cuenta de CD4 (glóbulos blancos) baja y una carga viral (cantidad de virus en sangre) alta corren un mayor riesgo de desarrollar una enfermedad renal. Las personas mayores con VIH también tienen un riesgo más elevado de padecer una insuficiencia renal.

Síntomas

Algunos de los síntomas de la insuficiencia renal pueden incluir:

• Orinar con más frecuencia de la habitual una orina descolorida, con menor frecuencia una orina más oscura, u orina con espuma o sangre
• Dificultad para orinar, o despertarse con frecuencia durante la noche para orinar
• Hinchazón de las piernas, pies, tobillos, cara y manos
• Fatiga excesiva
• Picazón o erupciones cutáneas
• Dificultad para respirar
• Falta de apetito o un sabor metálico en la boca
• Náuseas y vómitos
• Desmayos, mareos o dificultad para concentrarse
• Sentir demasiado frío
• Dolor de piernas, espalda o costado.

Causas

Las dos causas más comunes de insuficiencia renal son la tensión arterial alta (hipertensión) y la diabetes, una enfermedad en la que el cuerpo no puede controlar los niveles de azúcar en sangre.

Ciertos factores fuera del control del paciente, como antecedentes familiares de la enfermedad, un nacimiento prematuro y diversos traumatismos o lesiones pueden ser factores de riesgo para la insuficiencia renal. Los afroamericanos y los hispanos también tienen más riesgo de padecer insuficiencia renal.

El VIH en sí puede dañar los riñones, lo que se conoce como nefropatía asociada al VIH. Se cree que el virus la causa al infectar y dañar las células de los riñones. El daño renal por VIH puede ocurrir incluso en personas que toman medicamentos antirretrovirales.

Los medicamentos para el VIH y otros problemas de salud relacionados con el VIH también resultan agresivos para los riñones y, con el tiempo, pueden contribuir a la insuficiencia renal.

Los fármacos antirretrovirales que se han asociado con insuficiencia renal incluyen el Viread (tenofovir), el Crixivan (indinavir), el Reyataz (atazanavir),y, posiblemente, la Kaletra (lopinavir / ritonavir). No se recomienda que las personas con insuficiencia renal grave o terminal tomen Selzentry (maraviroc).

Otras enfermedades que pueden aumentar el riesgo de sufrir insuficiencia renal son la infección por hepatitis C, los cálculos renales, que bloquean el tracto urinario, la glomerulonefritis, una respuesta inflamatoria inmune a infecciones como la faringitis estreptocócica que puede dañar los riñones, y las reacciones alérgicas a antibióticos como la penicilina y la vancomicina.

El uso de drogas como la heroína y la cocaína y el uso excesivo de analgésicos que contienen ibuprofeno (Advil, Motrin), naproxeno (Aleve), aspirina o acetaminofén (Tylenol) también pueden contribuir a la insuficiencia renal.

Diagnóstico

Existen varias pruebas para determinar si una persona padece insuficiencia renal. Las más comunes son las pruebas de sangre y orina que miden la función renal.

Los análisis de sangre vigilan la tensión arterial (que puede aumentar en las personas con insuficiencia renal) y la cantidad de una sustancia llamada creatinina en sangre. La creatinina es un producto de desecho del metabolismo y los riñones tienen que filtrarla para eliminarla de la sangre. Unos niveles de creatinina en sangre altos pueden indicar una disfunción renal.

Los análisis de orina miden los niveles de proteínas en la orina. Cuando los riñones no funcionan bien, las proteínas comienzan a acumularse en la orina, junto con los glóbulos rojos y blancos. Generalmente, la presencia de niveles altos de proteínas o células sanguíneas en la orina indica la existencia de una enfermedad renal.

Hay pruebas adicionales que pueden incluir una ecografía, resonancia magnética o tomografía para ver los riñones. En algunos casos, se puede realizar una biopsia del riñón, prueba en la que se extrae una trocito de riñón y se examina al microscopio.

Según la Fundación Nacional del Riñón, las personas con VIH y con factores de riesgo de sufrir insuficiencia renal deberían hacerse pruebas que detecten la misma al menos una vez al año.

Para obtener más información sobre el tratamiento de la insuficiencia renal, por favor, vea la parte 2 de esta serie. Para obtener más información sobre el trasplante renal en personas con VIH, por favor consulte la parte 3 de esta serie.

However, one study that examined the efficacy of single versus double boosted protease inhibitors in adults with drug-resistant HIV found that double boosted protease inhibitors offered no additional benefits over single boosted.

Although antiretroviral therapy is usually highly successful at treating HIV, drug-resistant forms of the virus have emerged over time. Studies have suggested that about 15 percent of HIV strains show resistance to treatment with traditional antiretroviral drugs.

In some cases people have HIV that is resistant to all three of the main antiretroviral drug classes – nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors.

Newer Antiretroviral Drugs Are Effective For Treating Drug-Resistant HIV

A team of researchers in Spain found that four newer antiretroviral drugs – Isentress (raltegravir), Selzentry (maraviroc), Prezista (darunavir), and Intelence (etravirine) – safely and effectively treated people with drug-resistant HIV.

The small study examined people the researchers called “hard rescues” – patients with virologic failure, or a viral load (amount of virus in the blood) measuring greater than 50 copies per milliliter in two consecutive measurements, whose HIV was resistant to all three main antiretroviral classes.

Most of the patients (84 percent) were assigned to more than one of the new drugs, with 56 percent receiving more than two. In total, 84 percent received Isentress, 80 percent Prezista, 52 percent Selzentry, and 24 percent Intelence.

After 24 months, 78 percent of the study participants had undetectable viral loads, with a median CD4 (white blood cell) count of 634 cells per microliter.

There were no deaths during the study period, and none of the participants were hospitalized for opportunistic infections (infections that do not occur in individuals with healthy immune systems).

The researchers concluded that newer antiretrovirals are safe and effective for treatment of people with drug-resistant HIV.

Isentress Is Effective At Reducing Viral Loads In People With Highly Drug-Resistant HIV

A small study by the British Columbia Centre for Excellence in HIV/AIDS in Canada found that Isentress was capable of achieving viral suppression in up to 81 percent of highly drug-resistant HIV-positive patients.

Isentress is an integrase inhibitor, a relatively new class of antiretroviral drugs that work differently than most antiretrovirals. As a result, it can be effective against HIV strains that are resistant to more common antiretrovirals.

The study followed 112 individuals who were already treatment-experienced, with a median of 8 treatment switches before beginning treatment with Isentress.

At the end of the study, 81 percent of participants had achieved viral suppression – a viral load of 50 copies per milliliter or less – and participant CD4 cell counts increased a median of 15 percent over 17 months.

The researchers concluded that new antiretroviral drugs such as Isentress allow even patients with highly drug resistant HIV to successfully reach viral suppression.

Selzentry Is Safe And Effective In Treatment-Experienced Patients With Drug-Resistant HIV

Researchers in Italy conducted a small study to assess the effectiveness and safety of Selzentry in treatment-experienced patients with multi-drug-resistant HIV.

Selzentry is an entry inhibitor, a relatively new class of antiretrovirals that work by preventing HIV from entering human cells. Since it works differently than most antiretrovirals, it can be effective even against strains of HIV that are resistant to most antiretroviral drugs.

The study included 33 treatment-experienced patients with multi-drug-resistant HIV. After two months of treatment with Selzentry plus other antiretrovirals, 82 percent of study participants achieved viral suppression.

Participants also experienced notable increases in CD4 cell count, with a median increase of 10 cells per month.

Selzentry was used in combination with several different types of antiretrovirals, including boosted protease inhibitors such as Prezista; NNRTIs such as Intelence; and the integrase inhibitor Isentress. One study participant took Selzentry with Fuzeon (enfuvirtide).

In all cases and combinations, researchers concluded that Selzentry was both well-tolerated and effective in treating HIV-positive adults with multi-drug-resistant HIV.

CD4 Cell Counts Increase Faster During Treatment With Fuzeon

A small French study found that patients with drug-resistant HIV experienced greater CD4 cell count increases when Fuzeon was added to their optimized antiretroviral drug regimens.

Fuzeon is an entry inhibitor. Like Selzentry, it works by preventing HIV from entering and infecting human immune system cells.

During the study, half of the participants received a short, three-month course of Fuzeon in addition to an optimized antiretroviral drug regimen; the other half received the optimized regimen without Fuzeon.

After three months, participants who received Fuzeon had median CD4 cell counts that were 110 cells per microliter higher than participants who did not take Fuzeon.

Three months after the first group stopped taking Fuzeon, however, the two groups had the same median CD4 cell counts of 520 cells per microliter, suggesting that the immune system benefits of Fuzeon did not last once participants stopped taking it.

The two groups were equally successful at achieving viral suppression, indicating that adding Fuzeon did not provide additional improved viral control.

The researchers concluded that Fuzeon may have a beneficial effect on immune system restoration and that this effect is independent of its antiviral activity.

No Advantage Found In Treatment With Double Boosted Versus Single Boosted Protease Inhibitors

In a comparison between single boosted and double boosted protease inhibitor treatments, double boosted protease inhibitors were found to have no additional benefit over single boosted in people with HIV who were resistant to NNRTIs.

Boosting protease inhibitors is a method of increasing their effectiveness by administering Norvir (ritonavir) simultaneously. Norvir slows down the rate at which other protease inhibitors are broken down in the body, which keeps their concentrations in the blood higher.

The study was conducted by researchers at a hospital in Thailand and included 64 participants, none of whom had taken protease inhibitors before. All of the participants had previously exhibited resistance to treatment with NNRTIs.

Forty of the participants were given a single boosted protease inhibitor regimen of Kaletra (lopinavir/ritonavir), which contains Norvir. The rest received a double boosted regimen containing Reyataz (atazanavir), Invirase (saquinavir mesylate), and Norvir.

After 48 weeks, no difference was observed between the two treatment strategies in terms of effectiveness and side effects.

By the end of the study, 60 percent of participants taking the single boosted protease inhibitor achieved viral suppression versus 67 percent in the double boosted group. There were no differences in final CD4 counts or side effects such as raised cholesterol levels.

The researchers concluded that there was no added benefit to using a double boosted versus single boosted protease inhibitor regimen.

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.

Some of the studies found that HIV-related diseases and complications, such as osteoporosis, heart problems, and sexual dysfunction, are more prevalent in older adults with HIV.

However, several studies also showed positive results, including unexpected data showing HIV may not cause faster immune system and brain decline with age. Additional studies showed the benefits of exercise and strength training and the effectiveness of Selzentry (maraviroc) in older patients with HIV.

Postmenopausal HIV-Positive Women Are At Increased Risk Of Osteoporosis

A study of 35 postmenopausal women with HIV aged 45 or older revealed a high prevalence of the bone disease osteoporosis.

After measuring bone density in the spine and hip, researchers found that 18 percent of the women had osteoporosis and 59 percent had osteopenia, low bone density that can lead to osteoporosis.

For postmenopausal women over 50, rates of osteoporosis and osteopenia are usually around 7 percent and 40 percent, respectively.

The researchers were uncertain why HIV-positive women have higher rates of osteoporosis and suggested further study.

Higher Risk Of Heart Disease And Sexual Dysfunction, But Not Depression

A large German study compared the frequency of heart disease, sexual dysfunction, and depression in three groups of people over 50 years old.

The three groups consisted of HIV-positive people, HIV-negative people with diabetes, and a group of patients who had no chronic or progressive diseases.

In one arm of the study, researchers assessed the risk of heart disease in the three populations. They found that the HIV-positive patients were at a greater risk of heart disease than the patients without chronic or progressive diseases, but not as high a risk as participants with diabetes.

Additionally both the HIV-positive patients and HIV-negative patients with diabetes had significantly lower “good” cholesterol (HDL) levels than the patients without chronic or progressive diseases.

The German study also examined sexual difficulties in men in the three groups and found that moderate or severe sexual complaints were more often reported by HIV-positive patients (77 percent) than either the HIV-negative patients with diabetes (74 percent) or the patients without chronic or progressive diseases (63 percent), regardless of whether or not the patient had a stable partner.

However, there was a significant link between decreased sexual function and advanced age in all three of the groups.

In addition, the researchers investigated the rate of depression in the three groups. About a third of HIV-positive participants were classified as having a depressive disorder, which was similar to the other two groups.

The researchers found that socio-economic factors, such as the presence or absence of a stable relationship and employment, were the largest influences on development of depression.

HIV May Not Lead To Faster Brain Aging

An ongoing study at the University of California, San Francisco, is studying the brain function of men and women with HIV who are aged 60 years or older. So far, researchers have found that nearly half of the study participants (47 percent) have some degree of mental impairment: 5 percent of patients have dementia, 23 percent have mild mental impairment, and 19 percent have minor mental impairment that has no effect on daily functioning.

However, the scientists noted that these are similar to the rates found in younger HIV-positive adults, which contradicts the currently held view that HIV leads to faster brain aging.

The researchers believe that there may be a common factor that increases both the risk of mental impairment and early HIV-related mortality – in other words, adults who show HIV-related mental impairment may also be more likely to die at a younger age.

As a result, adults who have survived into old age with HIV would not be more prone to mental impairment than their younger counterparts.

The researchers plan to further investigate the possible connection between HIV-related mental impairment and early HIV mortality.

Age May Not Weaken The Immune System Of HIV-Positive Adults

This study investigated the relationship between HIV-related immune system deterioration and aging in patients with viral suppression. The study compared HIV-infected adults aged 55 years or older to people with HIV between the ages of 25 and 40. All participants had viral loads (amount of virus in the blood) of 50 copies per milliliter or less.

Researchers hypothesized that higher death rates in older HIV-positive adults, even those with viral suppression, might be due to immune system deterioration as people age.

They found that there was no clear relationship observed between age and decreased immune function. They also found that there were almost no significant age-associated immune changes, which surprised the researchers.

The results suggest that higher mortality in older HIV-positive adults may not be due to faster immune system degeneration.

Resistance Training Is Highly Effective In Older Adults With HIV

Another study demonstrated that after a year of resistance training, people with HIV ages 60 and older were able to achieve strength equal to people of the same age without HIV.

Researchers compared the effects of one year of resistance training on muscular strength, physical fitness, and body composition in older adults with and without HIV. Both groups of participants performed exercises for the major muscle groups twice a week.

Although people with HIV started off weaker and with less muscle than participants without HIV, they gained more strength faster. By the end of the study, there was no difference in strength between the two groups.

The results suggest that older adults with HIV can significantly improve their strength and body health to normal levels with regular resistance training.

Small Study Suggests Selzentry Is Safe And Effective In Older HIV-Positive Adults

A small study evaluated the safety and efficacy of Selzentry in six treatment-experienced patients with HIV who were over 60 years old.

Results showed that the medication was highly effective, with participants reaching viral suppression (viral load of less than 50 copies per milliliter) within a median of 1.5 months, with a median CD4 cell count increase of 10 cells per month.

In all cases, Selzentry was combined with other new antiretroviral medications, including Prezista (darunavir), Intelence (etravirine), and Isentress (raltegravir).

Selzentry was generally well-tolerated. However, the patients did exhibit a slight increase in triglycerides, a form of fat in the body that is associated with increased risk of heart disease.

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

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.

The new information states that Selzentry is contraindicated and should not be taken by individuals with severe kidney impairment or end-stage renal (kidney) disease (ESRD) who are taking strong CYP3A inhibitors or inducers, which includes the antiretroviral Norvir (ritonavir).

The FDA also recommends that patients with severe kidney impairment or ESRD not take Selzentry unless no alternative treatments are available.

CYP3A is a family of enzymes that break down Selzentry in the body. CYP3A inhibitors and inducers can affect the amount of Selzentry in the bloodstream.

Inducers include Norvir; carbamazepine (Tegretol), an anticonvulsant and mood stabilizer; the antibiotics rifampin and Mycobutin (rifabutin); and St. John’s wort.

Inhibitors include ketoconazole (Nizoral), itraconazole (Sporanox), and fluconazole (Diflucan), used to treat fungal infections; Tagamet or Tagamet HB (cimetidine), used to treat heartburn and stomach ulcers; the antibiotics clarithromycin (Biaxin), erythromycin, and troleandomycin; and grapefruit juice.

In addition, the FDA noted that individuals taking Selzentry who have impaired kidney function are at greater risk of postural hypotension, a drop in blood pressure due to a change in body position.

Postural hypotension could increase risk of heart problems, so the FDA recommends that these patients not take Selzentry unless other options are not available. If Selzentry is necessary, any patients experiencing symptoms of postural hypotension should have their dosage reduced to 150 mg twice daily.

The new label is the result of a study examining the effects of Selzentry in people with kidney impairment.

According to its prescribing information (pdf), the kidneys account for 25 percent of the total clearance of Selzentry by the body. As a result, in individuals with kidney impairment, Selzentry concentrations may increase in the bloodstream.

In addition to the new information for people with severe kidney impairment or ESRD, Pfizer, the manufacturer of Selzentry, also studied the effects of Selzentry in people with mild or moderate kidney impairment.

These results were similar to those of individuals with normal kidney function. The FDA made no new recommendations on dosage adjustment for individuals with mild or moderate kidney impairment, even if they are also taking strong CYP3A inhibitors or inducers.

Selzentry is a member of a relatively new class of antiretrovirals called entry inhibitors. Entry inhibitors work by preventing HIV from attaching to and entering healthy T cells in the body.

Generally, Selzentry is used by individuals who have been previously treated for HIV infection and have formed resistance to other antiretroviral medications.

For more information, please see the updated label for Selzentry, which will be available soon on the FDA website.

Selzentry was originally approved for treatment-experienced patients in 2007. Pfizer, Selzentry’s manufacturer, applied for its expanded use in September after receiving results from study 1026.

Study 1026 compared a 300 mg dose of Selzentry given twice daily in combination with Combivir (zidovudine/lamivudine) to treatment of Combivir and Sustiva (efavirenz) in treatment-naïve patients. Sustiva is an effective antiretroviral already approved as an option for patients undergoing treatment for the first time.

Selzentry specifically targets HIV strains that use a protein, called CCR5, to enter human T cells. Other strains of HIV use the CXCR4 protein and are not susceptible to the effects of Selzentry. It has been suggested that treatment-naïve patients are the most appropriate group to receive Selzentry because most are infected with CCR5-using HIV only.

Pfizer initially applied for Selzentry approval after week 48 results became available from study 1026. The reviewing FDA committee determined that the results showed a significant rate of virologic failure, or reemergence of a high viral load, observed in participants taking Selzentry. As a result, the committee recommended waiting for the completion of the study at week 96 to monitor the long-term changes in viral load. These results are considered to be a more accurate assessment of the efficacy of Selzentry use in treatment-naive patients and are included in Pfizer’s recent application.

A more sensitive test to determine the type of protein, CCR5 or CXCR4, used by a patient’s HIV strain was developed during the course of the study. This test established that 44 percent of the virological failures seen were due to improper administration to individuals infected with CXCR4-using HIV.

The results from week 96 indicated that Selzentry was both safe and effective as a first-line treatment. Participants taking Selzentry showed similar changes in viral load and CD4 cell counts to those taking Sustiva. The Antiviral Drugs Advisory Committee has now voted to recommend approval of Selzentry for use in treatment-naïve patients.

For more information, please read the Antiretroviral Drugs Advisory Committee Briefing Document available on the FDA Web site, as well as the press release on the Pfizer Web site.