Investigational Integrase Inhibitor Hits HIV Hard

RIO DE JANEIRO, April 13 -- The novel investigational drug raltegravir was highly effective at reducing the level of virus in their blood of sick HIV patients, many of them with AIDS, according to researchers here.

At the end of 24 weeks of treatment -- halfway through a planned 48 weeks -- up to two thirds of patients taking one of three doses of raltegravir had undetectable levels of virus in their blood, found Beatriz Grinsztejn, M.D., of Evandro Chagas Clinical Research Institute and the Oswaldo Cruz Foundation.

At the same time, only 13.3% of patients getting placebo reached fewer than 50 copies of viral RNA per milliliter of blood, considered the limit of detectability, Dr. Grinsztejn and colleagues reported in the April 14 issue of The Lancet.

The industry-sponsored phase IIB study is testing three doses of raltegravir - which blocks integration of the viral DNA into the host cell genome - in patients who are no longer responding to most HIV drugs.

The HIV/AIDS community is watching this and other trials carefully because raltegravir is the first of a new class of medications called integrase inhibitors that hold the promise of new types of treatments.

Indeed, unless unexpected side effects emerge or resistance arises, "raltegravir will have a major role in salvage therapy," said Pedro Cahn, M.D., Ph.D. and Omar Sued, M.D., both of Fundacin Huesped in Buenos Aires. Dr. Cahn is the incoming president of the International AIDS Society.

Drs. Cahn and Sued said the "encouraging" data on raltegravir, combined with similar reports on other novel drugs, mean that "clearly we are in a new area of antiretroviral therapy."

The current report follows interim reports on the drug from two continuing phase III trials, whose investigators reported similar results at the February Conference ON Retroviruses and Opportunistic Infections in Los Angeles. (CROI: Integrase Inhibitor 'Striking' in Early Results )

For this study, researchers in several centers recruited 178 HIV-positive volunteers with virological failure and documented resistance to several drugs. They were randomized to placebo or 200, 400, or 600 milligrams of raltegravir twice a day.

Patients were also given a so-called optimized background -- the best possible anti-retroviral regimen their physicians could assemble, given their resistance to a range of drugs.

At 24 weeks, Dr. Grinsztejn and colleagues reported, all the raltegravir patients had experienced sharp drops in viral load, compared with placebo and a large proportion in each arm had reached the level of detectability.

The study showed:

• 14 (11%) of the 133 patients in the raltegravir groups stopped therapy because of lack of efficacy, compared with 27 (60%) of the 45 patients on placebo.
• The mean drop in viral load from baseline was 1.80 log₁₀ copies per milliliter in the 200-milligram group - or by nearly a factor of 100.
• The corresponding figures for the 400- and 600-milligram groups were 1.87 and 1.84 log₁₀ copies per milliliter.
• In the placebo group, the mean reduction was 0.35 log₁₀ copies per milliliter.
• The differences were statistically significant at P