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Rapid onset and durable antiretroviral effect of raltegravir (MK-0518), a novel HIV-1 integrase inhibitor, as part of combination ART in treatment HIV-1 infected patients: 48-week data
Presented by Martin Markowitz, United States.
Markowitz M.1, Nguyen B.-Y.2, Gotuzzo E.3, Mendo F.4, Ratanasuwan W.5, Kovacs C.6, Wan H.2, Gilde L.2, Isaacs R.2, Teppler H.2, and the Protocol 004 Part II Study Team
1Aaron Diamond AIDS Research Center, New York, NY, United States, 2Merck Research Laboratories, West Point, PA, 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: To evaluate raltegravir vs efavirenz (EFV), combined with tenofovir/lamivudine (TFV/3TC), in ART-naive HIV-1-infected patients.
Methods: Multicenter, double-blind, randomized study of raltegravir (100, 200, 400, or 600 mg p.o. bid) vs EFV (600 mg qd) both with TFV/3TC. Patients with HIV-1 RNA ³5000 copies/mL and CD4+ T cells ³100/uL were monitored for safety, tolerability, and efficacy (HIV-1 RNA and CD4+ T cell count) over 48 weeks.
Results: 198 patients (mean age 36 years) were treated; 80% were male, 69% were non-white, and 34% had AIDS. Mean baseline HIV-1 RNA ranged from 4.6 to 4.8 log10 copies/mL. Proportions of patients achieving HIV-1 RNA <400 or <50 copies/mL at Weeks 24 and 48 are shown (non-completer=failure):
| | | | <400 copies/mL | <50 copies/mL | | Treatment Group (with TFV/3TC) | N | Week 24 | Week 48 | Week 24 | Week 48 | | Raltegravir bid | 100 mg | 39 | 95 (83,99) | 97 (87,100) | 87 (73,96) | 85 (70,94) | | | 200 mg | 40 | 85 (70,94) | 85 (70,94) | 85 (70,94) | 83 (67,93) | | | 400 mg | 41 | 98 (87,100) | 98 (87,100) | 93 (80,99) | 88 (74,96) | | | 600 mg | 40 | 95 (83,99) | 90 (76,97) | 95 (83,99) | 88 (73,96) | | Efavirenz qd | 600 mg | 38 | 95 (82,99) | 87 (72,96) | 92 (78,98) | 87 (72,96) |
All groups showed sustained ³2.2 log10 decline in HIV-1 RNA and similar increases in CD4+ T cells (144-221/uL). Patients in all raltegravir groups achieved RNA <50 copies/mL earlier than patients in the EFV group; by Week 24 all groups had similar responses which were sustained to Week 48. Drug-related clinical adverse experiences (AEs) were generally similar in all groups; nausea, dizziness and headache were most common. Laboratory AEs were infrequent. Raltegravir had no adverse effect on total or LDL cholesterol, or triglycerides. Neuropsychiatric AEs were significantly less frequent with raltegravir than with EFV. There were no drug-related serious AEs.
Conclusions: Raltegravir with TFV/3TC at all doses studied had potent and durable antiretroviral activity similar to EFV/3TC/TFV and was generally well-tolerated in ART-naive patients.
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