Human immunodeficiency virus (HIV)-infected South African patients (n=468) received blinded lamivudine or emtricitabine, stavudine, and either nevirapine or efavirenz (based on screening viral load). Baseline characteristics were analyzed in univariate and multivariate regression, to identify risk factors for hepatotoxicity (grade 3 or greater increase in serum aminotransferase levels). The occurrence of early hepatotoxicity was 17% in the nevirapine group and 0% in the efavirenz group and was balanced between the lamivudine and emtricitabine arms. Two subjects died of hepatic failure. Independent risk factors were body-mass index (BMI) <18.5, female sex, serum albumin level <35 g/L, mean corpuscular volume >85 fL, plasma HIV-1 RNA load <20,000 copies/mL, aspartate aminotransferase level <75 IU/L, and lactate dehydrogenase level <164 IU/L. The use of nevirapine in female patients with a low BMI should be discouraged.

Associations have been reported between an MDR1 variant and responses to nonnucleoside reverse-transcriptase inhibitors. We explored associations between MDR1, CYP2B6, and CYP3A polymorphisms and nevirapine hepatotoxicity. Among participants in a randomized study in South Africa (FTC-302), MDR1 3435C-->T was significantly associated with decreased risk of hepatotoxicity (risk ratio, 0.30; P=.016).

HE ADVENT OF HIGHLY ACTIVE antiretroviral therapy (HAART) dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, but limitations of HAART regimens include short plasma and intracellular half-life, drug-drug interactions, high pill burden, and adverse effects. In a metaanalysis of 23 prospective clinical trials with varied first-generation HAART regimens, suppression of HIV-1 RNA levels to less than or equal to 50 copies/mL at week 48 occurred in only 47% of treatment-naive patients. 1 Oncedaily HAART provides a strategy that should increase adherence and thereby Author Affiliations, Financial Disclosures, and Members of the FTC-301A Study Team are listed at the end of this article.

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The coformulation of EFV/FTC/TDF is bioequivalent to administration of its individual components.