Several studies presented at the 2010 International AIDS Conference found that newer antiretrovirals, such as Isentress and Selzentry, are safe and effective at treating even multi-drug-resistant HIV.

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.