OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of raltegravir vs efavirenz-based antiretroviral therapy after 96 weeks in treatment-naive patients with HIV-1 infection. METHODS: Multicenter, double-blind, randomized study of raltegravir (100, 200, 400, or 600 mg twice a day) vs efavirenz (600 mg every day), both with tenofovir/lamivudine (TDF/3TC), for 48 weeks, after which raltegravir arms were combined and all dosed at 400 mg twice a day. Eligible patients had HIV-1 RNA > or =5000 copies per milliliter and CD4 T cells > or =100 cells per microliter. RESULTS:One hundred ninety-eight patients were randomized and treated; 160 receivedraltegravir and 38 received efavirenz. At week 96, 84% of patients in both groups achieved HIV-1 RNA <400 copies per milliliter; 83% in the raltegravir group and 84% in the efavirenz group achieved <50 copies per milliliter (noncompleter = failure). Both groups showed similar increases in CD4 T cells (221 vs 232 cells/uL, respectively). An additional 2 patients (1 in each group) met the protocol definition of virologic failure between weeks 48 and 96; no known resistance mutations were observed in the raltegravir recipient; the efavirenz recipient had nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance mutations. Investigator reported drug-related clinical adverse events (AEs) were less frequent with raltegravir (51%) than efavirenz (74%). Drug-related AEs occurring in >10% of patients in either group were nausea in both groups and dizziness and headache in the efavirenz group. Laboratory AEs remained infrequent. Raltegravir had no adverse effect on total or low-density lipoprotein cholesterol or on triglycerides. Neuropsychiatric AEs remained less frequent with raltegravir (34%) than efavirenz (58%). There were no drug-related serious AEs in patients receiving raltegravir. CONCLUSIONS: In antiretroviral therapy-naive patients, raltegravir with TDF/3TC had potent antiretroviral activity, which was similar to efavirenz/TDF/3TC and was sustained to week 96. Raltegravir was generally well tolerated; drug-related AEs were less frequent in patients treated with raltegravir compared with efavirenz.
RCT Entities:
OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of raltegravir vs efavirenz-based antiretroviral therapy after 96 weeks in treatment-naive patients with HIV-1 infection. METHODS: Multicenter, double-blind, randomized study of raltegravir (100, 200, 400, or 600 mg twice a day) vs efavirenz (600 mg every day), both with tenofovir/lamivudine (TDF/3TC), for 48 weeks, after which raltegravir arms were combined and all dosed at 400 mg twice a day. Eligible patients had HIV-1 RNA > or =5000 copies per milliliter and CD4 T cells > or =100 cells per microliter. RESULTS: One hundred ninety-eight patients were randomized and treated; 160 received raltegravir and 38 received efavirenz. At week 96, 84% of patients in both groups achieved HIV-1 RNA <400 copies per milliliter; 83% in the raltegravir group and 84% in the efavirenz group achieved <50 copies per milliliter (noncompleter = failure). Both groups showed similar increases in CD4 T cells (221 vs 232 cells/uL, respectively). An additional 2 patients (1 in each group) met the protocol definition of virologic failure between weeks 48 and 96; no known resistance mutations were observed in the raltegravir recipient; the efavirenz recipient had nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance mutations. Investigator reported drug-related clinical adverse events (AEs) were less frequent with raltegravir (51%) than efavirenz (74%). Drug-related AEs occurring in >10% of patients in either group were nausea in both groups and dizziness and headache in the efavirenz group. Laboratory AEs remained infrequent. Raltegravir had no adverse effect on total or low-density lipoprotein cholesterol or on triglycerides. Neuropsychiatric AEs remained less frequent with raltegravir (34%) than efavirenz (58%). There were no drug-related serious AEs in patients receiving raltegravir. CONCLUSIONS: In antiretroviral therapy-naive patients, raltegravir with TDF/3TC had potent antiretroviral activity, which was similar to efavirenz/TDF/3TC and was sustained to week 96. Raltegravir was generally well tolerated; drug-related AEs were less frequent in patients treated with raltegravir compared with efavirenz.
Authors: Manuel Tsiang; Gregg S Jones; Anita Niedziela-Majka; Elaine Kan; Eric B Lansdon; Wayne Huang; Magdeleine Hung; Dharmaraj Samuel; Nikolai Novikov; Yili Xu; Michael Mitchell; Hongyan Guo; Kerim Babaoglu; Xiaohong Liu; Romas Geleziunas; Roman Sakowicz Journal: J Biol Chem Date: 2012-04-25 Impact factor: 5.157
Authors: Daniel A Donahue; Richard D Sloan; Björn D Kuhl; Tamara Bar-Magen; Susan M Schader; Mark A Wainberg Journal: Antimicrob Agents Chemother Date: 2009-12-28 Impact factor: 5.191
Authors: Roy T Steigbigel; David A Cooper; Hedy Teppler; Joseph J Eron; Jose M Gatell; Princy N Kumar; Jurgen K Rockstroh; Mauro Schechter; Christine Katlama; Martin Markowitz; Patrick Yeni; Mona R Loutfy; Adriano Lazzarin; Jeffrey L Lennox; Bonaventura Clotet; Jing Zhao; Hong Wan; Rand R Rhodes; Kim M Strohmaier; Richard J Barnard; Robin D Isaacs; Bach-Yen T Nguyen Journal: Clin Infect Dis Date: 2010-02-15 Impact factor: 9.079