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Sustained antiretroviral efficacy of raltegravir as part of combination ART in treatment-naive HIV-1 infected patients: 144-week data
E. Gotuzzo1, B.-Y. Nguyen2, M. Markowitz3, F. Mendo4, W. Ratanasuwan5, C. Kovacs6, G. Prada7, J. Morales-Ramirez8, C. Crumpacker9, C. Lu2, D. Brown2, R. Isaacs2, K. Strohmaier2, R. Danovich2, H. Teppler2, and the Protocol 004 Part II Study Team
1Hospital Nacionale Cayetano Heredia, Lima, Peru, 2Merck Research Laboratories, West Point, United States, 3Aaron Diamond AIDS Research Center, New York, United States, 4Hospital Nacionale Edgardo Rebagliati, Lima, Peru, 5Siriraj Hospital, Bangkok, Thailand, 6Canadian Immunodeficiency Research Collaborative, Toronto, Canada, 7Fundación Santafe de Bogota University Hospital, Bogota, Colombia, 8Clinical Research Puerto Rico, Inc., San Juan, Puerto Rico, 9Beth Israel Deaconess Medical Center, Boston, United States
Background: Phase II study evaluating long-term efficacy, safety and tolerability of raltegravir (RAL), an HIV-1 integrase inhibitor, vs efavirenz (EFV), combined with tenofovir/lamivudine (TDF/3TC), in ART-naive HIV-1-infected patients (pts).
Methods: Multicenter, double-blind, randomized study evaluating RAL, 400mg bid vs EFV 600mg qd both with TDF/3TC, in ART-naïve pts with HIV-1 RNA ≥5000 copies/mL and CD4+ T-cells ≥100/uL. This abstract presents complete 144-week data. Note RAL was dose ranging (100, 200, 400, or 600mg bid) for first 48 weeks.
Results: 198 pts were randomized and treated; 160 pts received RAL, 38 received EFV. Baseline information and dose-ranging results to week 96 have been presented previously. At week 144, 80% vs 76% sustained HIV-1 RNA < 400 copies/mL, and 78% vs 76% sustained < 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 (252 vs 233/uL, respectively). Three pts met the protocol definition of virologic failure after week 96, 2 in the RAL group and 1 in the EFV group; resistance analysis is ongoing. Cumulative rates of drug-related clinical adverse experiences (AEs) remained less frequent in the RAL vs EFV group (54% vs 76%, respectively). The most common (eg. occurring in >10% of total pts) drug-related AEs were nausea, dizziness and headache; these were generally similar in both groups. Laboratory AEs remained infrequent. RAL had minimal effect on total or LDL cholesterol, or triglycerides. Cumulative neuropsychiatric AEs remained less frequent with RAL (35%) than EFV (61%). There were no drug-related serious AEs in pts receiving RAL.
Conclusions: In ART-naïve pts, RAL with TDF/3TC had potent and durable antiretroviral activity, which was similar to EFV/TDF/3TC and was sustained to week 144. RAL was generally well tolerated; drug related AEs were less frequent in pts treated with RAL compared to EFV.
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