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Sustained antiretroviral efficacy of raltegravir as part of combination ART in treatment-naive HIV-1 infected patients: 96-week data
Presented by Martin Markowitz, United States.
M. Markowitz1, B.-Y. Nguyen2, E. Gotuzzo3, F. Mendo4, W. Ratanasuwan5, C. Kovacs6, H. Wan2, H. Campbell2, R. Isaacs2, H. Teppler2, and the Protocol 004 Part II Study Team
1Aaron Diamond AIDS Research Center, Rockefeller University, New York, United States, 2Merck Research Laboratories, West Point, United States, 3Hospital Nacionale Cayetano Heredia, Lima, Peru, 4Hospital Nacionale Edgardo Rebagliati, Lima, Peru, 5Siriraj Hospital, Bangkok, Thailand, 6Canadian Immunodeficiency Research Collaborative, Toronto, Canada
Objectives: Phase II study evaluating efficacy, safety and tolerability of raltegravir (RAL), an HIV-1 integrase inhibitor, vs efavirenz (EFV), combined with tenofovir/lamivudine (TFV/3TC), in ART-naive HIV-1-infected patients (pts).
Methods: Multicenter, double-blind, randomized study evaluating RAL (100, 200, 400, or 600mg bid) vs EFV (600mg qd) both with TFV/3TC for 48 weeks, after which RAL doses were consolidated to 400mg bid. Eligible pts had HIV-1 RNA ³5000 copies/mL and CD4+ T-cells ³100/uL. This abstract presents complete 96 week data (HIV-1 RNA levels and CD4+ T-cell count) for RAL groups combined vs EFV.
Results: 198 pts were randomized and treated; 160 pts received RAL, 38 received EFV. Baseline information and dose-ranging results to week 48 have been presented previously. At week 96, 84% vs 84% achieved HIV-1 RNA <400 copies/mL, and 83% vs 84% achieved <50 copies/mL in the RAL and EFV groups, respectively (non-completer=failure). Both RAL and EFV groups showed similar increases in CD4+ T-cells (220 vs 232/uL, respectively). Two patients met the protocol definition of virologic failure after week 48, 1 in each group; no known RAL resistance mutations were observed. Drug-related clinical adverse experiences (AEs) were less frequent in the RAL vs EFV group (51% vs 74%, respectively). The most common (eg. occurring in >10% of total pts) drug-related AEs were nausea, dizziness and headache; and were generally similar in both groups. Laboratory AEs remained infrequent. RAL had no adverse effect on total or LDL cholesterol, or triglycerides. Neuropsychiatric AEs remained less frequent with RAL (16%) than EFV (32%). There were no drug-related serious AEs in patients receiving RAL.
Conclusions: In ART-naïve pts, RAL with TFV/3TC had potent antiretroviral activity, which was similar to EFV/3TC/TFV and was sustained to week 96. RAL was generally well tolerated; drug related AEs were observed to be less frequent in patients treated with RAL compared to EFV.
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