Background:  MK-0518 is a novel and potent HIV-1 integrase inhibitor. This study evaluates MK-0518 in HIV-infected patients with HIV RNA level >5000 copies/mL and documented genotypic/phenotypic resistance to each of the 3 classes of oral ART.

Methods:  Multi-center, double-blind, randomized study to evaluate the safety and efficacy of MK-0518 (200, 400, or 600 mg orally twice daily) vs placebo, both plus optimized background therapy (OBT). Since atazanavir (ATV) increases MK-0518 plasma concentrations, there are 2 sub-studies:  (A) patients receiving OBT without ATV, and (B) patients receiving OBT with ATV. Patients were closely monitored for safety and ART effect.

Results:  At this interim analysis, 116 patients were enrolled in sub-study A and 16 in sub-study B. The median duration for prior use of ART was ~10 years for both groups. The mean baseline HIV RNA ranged from 4.71 to 4.81 log₁₀ copies/mL. Based on phenotypic resistance testing at baseline, ~30% of patients had no active ART in their OBT. At week 8, the percentage of patients with HIV RNA level <400 copies/mL (observed data) is summarized in the table. At week 8, 63% to 67% of patients receiving MK-0518 treatment vs 8% receiving placebo had HIV RNA <50 copies/mL. The most common (³5% in any treatment group) drug-related adverse experiences were diarrhea, nausea, vomiting, fatigue, headache, flushing, injection site reaction, and pruritus; these were comparable between the MK-0518 and control groups. There were no dose-related adverse experiences and no discontinuations.

.

Conclusions:  In this preliminary analysis of patients failing current therapies and with triple-class resistant virus, the HIV-1 integrase inhibitor, MK-0518 at all doses in combination with OBT had potent antiretroviral activity and was generally well-tolerated.