Sustained antiretroviral effect of raltegravir after 96 weeks of combination therapy in treatment-naive patients with HIV-1 infection.
OBJECTIVE
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.
Markowitz
Martin
M
Aaron Diamond AIDS Research Center, New York, NY, USA.
Nguyen
Bach-Yen
BY
Gotuzzo
Eduardo
E
Mendo
Fernando
F
Ratanasuwan
Winai
W
Kovacs
Colin
C
Prada
Guillermo
G
Morales-Ramirez
Javier O
JO
Crumpacker
Clyde S
CS
Isaacs
Robin D
RD
Campbell
Havilland
H
Strohmaier
Kim M
KM
Wan
Hong
H
Danovich
Robert M
RM
Teppler
Hedy
H
D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000068898:Raltegravir Potassium
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; C098320:efavirenz