Class-sparing regimens for initial treatment of HIV-1 infection.

TitleClass-sparing regimens for initial treatment of HIV-1 infection.
Publication TypeJournal Article
Year of Publication2008
AuthorsRiddler SA, Haubrich R, A DiRienzo G, Peeples L, Powderly WG, Klingman KL, Garren KW, George T, Rooney JF, Brizz B, Lalloo UG, Murphy RL, Swindells S, Havlir D, Mellors JW
Corporate AuthorsAIDS Clinical Trials Group Study A5142 Team
JournalN Engl J Med
Volume358
Issue20
Pagination2095-106
Date Published2008 May 15
ISSN1533-4406
KeywordsAdolescent, Adult, Benzoxazines, Drug Resistance, Viral, Drug Therapy, Combination, Female, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Kaplan-Meier Estimate, Lopinavir, Male, Middle Aged, Mutation, Prospective Studies, Pyrimidinones, Reverse Transcriptase Inhibitors, Ritonavir, RNA, Viral, Treatment Failure
Abstract

BACKGROUND: The use of either efavirenz or lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors (NRTIs) is recommended for initial therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection, but which of the two regimens has greater efficacy is not known. The alternative regimen of lopinavir-ritonavir plus efavirenz may prevent toxic effects associated with NRTIs.

METHODS: In an open-label study, we compared three regimens for initial therapy: efavirenz plus two NRTIs (efavirenz group), lopinavir-ritonavir plus two NRTIs (lopinavir-ritonavir group), and lopinavir-ritonavir plus efavirenz (NRTI-sparing group). We randomly assigned 757 patients with a median CD4 count of 191 cells per cubic millimeter and a median HIV-1 RNA level of 4.8 log10 copies per milliliter to the three groups.

RESULTS: At a median follow-up of 112 weeks, the time to virologic failure was longer in the efavirenz group than in the lopinavir-ritonavir group (P=0.006) but was not significantly different in the NRTI-sparing group from the time in either of the other two groups. At week 96, the proportion of patients with fewer than 50 copies of plasma HIV-1 RNA per milliliter was 89% in the efavirenz group, 77% in the lopinavir-ritonavir group, and 83% in the NRTI-sparing group (P=0.003 for the comparison between the efavirenz group and the lopinavir-ritonavir group). The groups did not differ significantly in the time to discontinuation because of toxic effects. At virologic failure, antiretroviral resistance mutations were more frequent in the NRTI-sparing group than in the other two groups.

CONCLUSIONS: Virologic failure was less likely in the efavirenz group than in the lopinavir-ritonavir group. The virologic efficacy of the NRTI-sparing regimen was similar to that of the efavirenz regimen but was more likely to be associated with drug resistance. (ClinicalTrials.gov number, NCT00050895 [ClinicalTrials.gov].).

DOI10.1056/NEJMoa074609
Alternate JournalN. Engl. J. Med.
PubMed ID18480202
PubMed Central IDPMC3885902
Grant ListAI 060354 / AI / NIAID NIH HHS / United States
AI 064086 / AI / NIAID NIH HHS / United States
AI 068634 / AI / NIAID NIH HHS / United States
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UL1 TR000454 / TR / NCATS NIH HHS / United States
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