ICAAC: Elvitegravir Study Underlines Need for Several HIV Drugs

CHICAGO, Sept. 20 -- The experimental integrase inhibitor elvitegravir induces a swift reduction in HIV levels but needs an optimized background regimen, researchers emphasized.

The finding, from a randomized phase II dose-finding study of the drug, re-emphasizes the need for HIV regimens to contain more than a single active medication, according to Andrew Zolopa, M.D., of Stanford University.

And for patients with considerable treatment experience, drugs from new classes work better than those from classes that have been tried before -- even if genetic testing shows they remain active, Dr. Zolopa told attendees at the Interscience Conference on Anti-microbial Agents and Chemotherapy here.

Indeed, among patients in this study who also got the entry inhibitor enfuvirtide (Fuzeon), the lowering of HIV levels was maintained throughout the 24 weeks of the study.

"The main message here is that having an agent from a new class is better than having one from a recycled class, even if it is considered active," Dr. Zolopa said.

The study was designed as a non-inferiority study of elvitegravir, boosted with ritonavir, compared with protease inhibitors. All of the 269 patients in the study were on an optimized background regimen containing non-nucleoside or nucleoside reverse transcriptase inhibitors.

Some patients were also allowed to use enfuvirtide for the first time during the study, Dr. Zolopa said, and it was on those patients that he focused at this meeting.

The study tested three different doses of elvitegravir, but Dr. Zolopa discussed only the 125-milligram daily dose in comparison with protease inhibitors. The study's primary endpoint was the change from baseline in the level of HIV.

At 24 weeks, patients getting elvitegravir did significantly better overall than those on protease inhibitors -- posting a decline of 1.7 log₁₀ copies of viral RNA per milliliter of plasma, compared with a drop of 1.2 log₁₀ copies. The difference was significant at P=0.02.

But for those using enfuvirtide for the first time, the declines were much sharper -- a drop of 1.6 log₁₀ copies among patients on protease inhibitors and 2.6 log₁₀ copies for those getting elvitegravir.

Moreover, among patients without an active drug in their background, elvitegravir caused a sharp drop in HIV viral load within a few days of starting therapy, but by 24 weeks the virus had rebounded almost to baseline levels. The net drop in viral load was 0.7 log₁₀ copies.

On the other hand, both the protease inhibitors and elvitegravir -- combined with a first use of enfuvirtide -- showed an immediate sharp drop that persisted for the entire study period, Dr. Zolopa said.

"If there's no active drug in the background, we see a rapid drop but also a rebound," Dr. Zolopa said.

The "checkmark-like response curve" when the background regimen is feeble is especially revealing, said Roy Gulick, M.D., of Weill Medical College of Cornell University in New York, a senior HIV researcher who was not involved in this study.

He said it clearly shows that a single active drug is not enough to knock down the virus and keep it knocked down.

For clinicians, he said, the study is a "great way to illustrate that point."