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Title: Raltegravir Efficacy Challenging Current Theories on How HIV Replicates: Presented at IAS

"Raltegravir Efficacy Challenging Current Theories on How HIV Replicates: Presented at IAS"

By Rachel Parratt SYDNEY, AUSTRALIA -- July 25, 2007-- Phase 2 results from a study of a new HIV integrase inhibitor -- raltegravir (MK-0518) -- show a 70% reduction in viral load at onset of the second phase of HIV viral production compared with efavirenz. "These data challenge current theories, suggesting that viral production during the second phase does not originate from long-lived HIV-infected cells," commented J. Murray, Researcher, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. These findings were presented here on July 24th in an oral presentation at the 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention. Mathematical modeling put forward to explain these HIV viral dynamic observations suggests that second-phase virus comes from cells that have been newly infected by long-lived infected cells or from activation of latently infected cells with HIV DNA. Raltegravir may inhibit these new rounds of HIV infection more effectively than other drugs. This particular process is unaffected by reverse transcriptase inhibitors and protease inhibitors. Part 1 of this protocol included 9 days of monotherapy in antiretroviral (ART)-naive HIV patients receiving one of four twice-daily doses of raltegravir (100 mg, 200 mg, 400 mg, and 600 mg), with eight patients in each dose group. Part 2 consisted of 48 weeks of treatment with raltegravir or efavirenz in combination with tenofovir and lamivudine. Each raltegravir dose group achieved HIV RNA <50 copies/mL significantly faster compared with efavirenz at 15 days ([P <=.047), 29 days (P <=.003), and 57 days (P <=.006).

In addition, at the start of part 2 of the study, HIV RNA levels were 70% lower for raltegravir compared with efavirenz (P <.0001).

Overall, adverse events were similar across treatment groups, with no dose-related toxicities. Treatment-related clinical adverse effects were less common with raltegravir compared with efavirenz (48% vs 71%). Neuropsychiatric symptoms, such as nightmares and depression, were also less common with raltegravir compared with efavirenz. Grade 3 and 4 laboratory abnormalities were uncommon, and raltegravir had a neutral affect on serum lipids.

Funding for this study was provided by Merck.

[Presentation title: The Integrase Inhibitor Raltegravir Alters Viral Decay Kinetics of HIV, Significantly Reducing the Second Phase and Challenging Current Hypotheses of Viral Replication. Abstract TUAB103]

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