Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy.

TitleAbacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy.
Publication TypeJournal Article
Year of Publication2009
AuthorsSax PE, Tierney C, Collier AC, Fischl MA, Mollan K, Peeples L, Godfrey C, Jahed NC, Myers L, Katzenstein D, Farajallah A, Rooney JF, Ha B, Woodward WC, Koletar SL, Johnson VA, P Geiseler J, Daar ES
Corporate AuthorsAIDS Clinical Trials Group Study A5202 Team
JournalN Engl J Med
Volume361
Issue23
Pagination2230-40
Date Published2009 Dec 3
ISSN1533-4406
KeywordsAdenine, Adolescent, Adult, Analysis of Variance, Anti-HIV Agents, CD4 Lymphocyte Count, Deoxycytidine, Dideoxynucleosides, Double-Blind Method, Drug Combinations, Drug Resistance, Viral, Emtricitabine, Female, Fractures, Bone, HIV Infections, HIV-1, Humans, Lamivudine, Male, Middle Aged, Organophosphonates, RNA, Viral, Tenofovir, Therapeutic Equivalency, Time Factors, Treatment Failure, Viral Load, Young Adult
Abstract

BACKGROUND: The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.

METHODS: In a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or > or = 200 copies per milliliter at or after 24 weeks).

RESULTS: A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir-lamivudine group versus 26 (7%) in the tenofovir DF-emtricitabine group. The time to the first adverse event was also shorter in the abacavir-lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.

CONCLUSIONS: In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine. (ClinicalTrials.gov number, NCT00118898.)

DOI10.1056/NEJMoa0906768
Alternate JournalN. Engl. J. Med.
PubMed ID19952143
PubMed Central IDPMC2800041
Grant List1U01 A1069423-01 / / PHS HHS / United States
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