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New Drugs And Simplified Treatments Demonstrate Potential For Treating HIV (AIDS 2010)

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Published: Jul 20, 2010 4:01 pm
New Drugs And Simplified Treatments Demonstrate Potential For Treating HIV (AIDS 2010)

Researchers presented results of five studies involving new HIV treatment regimens yesterday as part of the 2010 International AIDS Conference in Vienna, Austria. Three of the studies involved simplified treatments meant to reduce side effects, and the other two studies presented clinical trial results for potential new antiretrovirals.

The studies, which yielded mostly positive results, illustrate the growing variety of treatment and medication options for people with HIV.

The three studies involving new treatment regimens all use Isentress (raltegravir), an integrase inhibitor approved by the United States Food and Drug Administration in 2007.

Integrase inhibitors are a relatively new class of drugs. They work by blocking the protein the virus uses to insert its DNA into the DNA of a healthy cell, thus preventing HIV from replicating. Isentress is currently the only approved integrase inhibitor.

In one study, Isentress was evaluated in a simplified two-drug combination treatment with Kaletra (lopinavir/ritonavir), a protease inhibitor. Two other studies tested the efficacy of replacing protease inhibitors with Isentress.

Protease inhibitors often increase cholesterol levels, which increases a patient’s risk of developing heart disease. Researchers predicted that switching to Isentress would reduce the risk of heart disease.

In all three studies, the new regimens involving Isentress have so far successfully suppressed the virus, produced few side effects, and decreased cholesterol levels in people with HIV.

The other two studies tested new drugs in Phase 2 development. Both drugs have demonstrated short-term efficacy and safety. One of the drugs is a CCR5 antagonist, like Selzentry (maraviroc). The other is a new integrase inhibitor, like Isentress.

Study Of The Two-Drug Combination Of Kaletra And Isentress

A 96-week-long Phase 3 study is currently assessing the safety and efficacy of taking Kaletra with Isentress. The new combination is compared to Kaletra plus Truvada (emtricitabine/tenofovir), which contains two reverse transcriptase inhibitors.

The study participants are all treatment-naïve, meaning they have not taken antiretroviral medications before.

The 48-week study results revealed that the combination of Kaletra and Isentress suppressed the virus as effectively as Kaletra plus Truvada. The treatment was well tolerated, and the most common side effects were diarrhea and high cholesterol. High cholesterol has been associated with protease inhibitors like Kaletra.

Researchers concluded that the two-drug combination of Kaletra and Isentress is promising as an effective treatment for HIV.

The Kaletra/Isentress treatment combination is unusual because it consists of only two medications and does not involve reverse transcriptase inhibitors.

The current regimen for people with HIV who are beginning treatment consists of three ART drugs: two reverse transcriptase inhibitors (such as those contained in Truvada) and a third drug, usually a protease inhibitor (such as Kaletra).

However, reverse transcriptase inhibitors have been associated with lipodystrophy, a side effect in which fat gets redistributed abnormally on the body. Changes in fat distribution can lead to changes in body shape and can also cause cardiovascular disease. As a result, researchers have experimented with antiretroviral regimens, such as the Kaletra/Isentress combination, that do not contain reverse transcriptase inhibitors.

The trial is ongoing but is no longer recruiting participants.

Replacement Of Protease Inhibitors With Once Or Twice Daily Isentress

A Phase 4 study evaluated the switch from a protease inhibitor regimen to a once or twice daily dosage of Isentress, an integrase inhibitor. The trial followed 222 participants with HIV for 24 weeks.

Researchers hoped switching to Isentress would lower participants’ cholesterol levels. In addition, Isentress is currently given twice daily. If effective, a once daily dosage would decrease treatment burdens for patients.

Researchers measured the effectiveness of the once daily dosage and monitored the patients’ cholesterol levels after switching from the protease inhibitor regimen.

Replacing the protease inhibitor regimen with Isentress was effective in all patients except in those who had previously demonstrated resistance to reverse transcriptase inhibitors. The once daily dosage of Isentress performed slightly worse than twice daily dosing.

In addition, as predicted, the patients’ cholesterol levels were significantly lowered after the switch to Isentress.

The study, sponsored by Hospital Carlos III in Madrid, is ongoing and currently recruiting participants.

Replacement Of Protease Inhibitors With Isentress

A 48-week Phase 3 study has been completed that compared patients taking protease inhibitors to those who switched to Isentress, an integrase inhibitor. The participants in both groups of the study started with low viral loads (amount of HIV in the blood).

At 48 weeks, the two regimens were similarly effective at maintaining low viral loads. Additionally, switching to Isentress effectively lowered cholesterol levels in patients.

There was a slight increase in the number of patients experiencing side effects. Side effects that led to treatment discontinuation occurred in 4 percent of patients treated with the Isentress regimen versus 2 percent of those on the protease inhibitor regimen.

Study Of A New CCR5/CCR2 Antagonist, TBR-652

Tobira Therapeutics completed a Phase 2 study of a possible new treatment, TBR-652, a dual CCR5/CCR2 antagonist.

CCR5/CCR2 antagonists work by blocking the CCR5 and CCR2 proteins on the outside of immune cells. When these proteins are blocked, the drug prevents HIV from attaching to and infecting the cells. Selzentry is the only currently approved CCR5 antagonist.

The study tested the antiviral ability, safety, and tolerability of TBR-652 taken once daily for 10 days. This is the first study of TBR-652 that has tested the medication on people with HIV.

A previous Phase 1 trial showed that the drug was well tolerated in HIV-negative subjects. The 54 HIV-positive participants in the Phase 2 trial also tolerated the drug well; there were no serious side effects or deaths.

Additionally, when TBR-652 was taken as the sole antiretroviral medication, the researchers reported significant antiviral activity, as measured by viral load.

“Our unique, dual CCR5/CCR2 investigational drug may provide a new strategy that would complement the well-established benefits of currently available virus-suppressing treatments for HIV,” said David Martin, Senior Vice President of Drug Development and Regulatory Affairs for Tobira Therapeutics in a press release.

The drug will require further trials at longer durations to determine whether it is a viable treatment option.

Study Of A New Integrase Inhibitor, S/GSK1349572

Shionogi-GlaxoSmithKline Pharmaceuticals is testing a new integrase inhibitor, S/GSK1349572, in an ongoing 24-week Phase 2b study on patients who are resistant to the integrase inhibitor Isentress.

The results through Day 11 have revealed that most of the subjects have tolerated the new drug well. The most commonly observed side effects were diarrhea and insomnia.

The study continues to observe the efficacy of the new integrase inhibitor against a variety of HIV-variants resistant to Isentress.

The trial is currently recruiting participants.

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

Photo by Lee Nachtigal on Flickr – some rights reserved.
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