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

Authors

Riddler SA, Haubrich R, DiRienzo AG, et al.

Institution

University of Pittsburgh, Pittsburgh, USA. riddler@dom.pitt.edu

Source

N Engl J Med 2008 May 15; 358(20) :2095-106.

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].).

Mesh

Adolescent
Adult
Benzoxazines
Drug Resistance, Viral
Drug Therapy, Combination
Female
HIV Infections
HIV Protease Inhibitors
HIV-1
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Mutation
Prospective Studies
Pyrimidinones
RNA, Viral
Reverse Transcriptase Inhibitors
Ritonavir
Treatment Failure

Language

eng

Pub Type(s)

Clinical Trial, Phase III Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural

PubMed ID

18480202

Content Manager

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