Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection

BACKGROUND Regimes containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimes containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited. METHODS This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine - lamivudine - abacavir, zidovudine - lamivudine plus efavirenz, and zidovudine - lamivudine - abacavir plus efavirenz. RESULTS We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log(10) (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P < 0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P ≤ 0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups. CONCLUSIONS In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides.