Intensification of a triple-nucleoside regimen with tenofovir or efavirenz in HIV-1-infected patients with virological suppression.

TitleIntensification of a triple-nucleoside regimen with tenofovir or efavirenz in HIV-1-infected patients with virological suppression.
Publication TypeJournal Article
Year of Publication2007
AuthorsGulick RM, Lalama CM, Ribaudo HJ, Shikuma CM, Schackman BR, Schouten J, Squires KE, Koletar SL, Pilcher CD, Reichman RC, Klingman KL, Kuritzkes DR
JournalAIDS
Volume21
Issue7
Pagination813-23
Date Published2007 Apr 23
ISSN0269-9370
KeywordsAdenine, Adult, Aged, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Benzoxazines, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, Genotype, HIV Infections, HIV-1, Humans, Male, Middle Aged, Organophosphonates, Patient Compliance, Reverse Transcriptase Inhibitors, RNA, Viral, Tenofovir, Treatment Outcome, Viral Load
Abstract

OBJECTIVE: To compare a quadruple-nucleoside with an efavirenz-containing regimen for treatment of HIV-1 infection.

DESIGN: A randomized, open-label study of the AIDS Clinical Trials Group (ACTG).

METHODS: Subjects receiving zidovudine/lamivudine/abacavir on ACTG 5095 with HIV-1 RNA less than 200 copies/ml were randomly assigned to intensify either with tenofovir or efavirenz. Subjects were followed for time to treatment failure, defined as either virological failure or treatment discontinuation. Analyses were intent-to-treat.

RESULTS: One hundred and seventy subjects (21% women; 56% non-white) entered the study. At baseline, 95 and 73% had HIV-1-RNA levels less than 200 and 50 copies/ml, respectively; the median CD4 cell count was 453 cells/microl. Over a median 79 weeks follow-up, 165 (97%) completed the study, three (2%) discontinued, and two (1%) died. Treatment failure occurred in 31 subjects: 18 (21%) (quadruple nucleosides) and 13 (15%) (efavirenz-containing regimen); however the failure-time curves crossed and demonstrated a non-constant treatment effect over time, characterized by more early treatment failures on the efavirenz-containing regimen and more late treatment failures on the four-nucleoside regimen. HIV-1 RNA remained suppressed in more than 88% of subjects to less than 200 copies/ml and in more than 78% to less than 50 copies/ml at weeks 24, 48, and 72, without differences by treatment arm. There were no significant differences between the regimens in CD4 cell increases, time to new grade 3/4 adverse events, or adherence.

CONCLUSION: The safety, tolerability, and efficacy of the four-nucleoside regimen were not significantly different from the efavirenz-containing regimen. These pilot data support further investigation of the quadruple-nucleoside regimen.

DOI10.1097/QAD.0b013e32805e8753
Alternate JournalAIDS
PubMed ID17415036
Grant ListAI 01781 / AI / NIAID NIH HHS / United States
AI 25859 / AI / NIAID NIH HHS / United States
AI 25868 / AI / NIAID NIH HHS / United States
AI 25879 / AI / NIAID NIH HHS / United States
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AI 34832 / AI / NIAID NIH HHS / United States
AI 38855 / AI / NIAID NIH HHS / United States
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AI 39156 / AI / NIAID NIH HHS / United States
AI 42848 / AI / NIAID NIH HHS / United States
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AI 46339 / AI / NIAID NIH HHS / United States
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AI 46386 / AI / NIAID NIH HHS / United States
AI 50410 / AI / NIAID NIH HHS / United States
AI 51966 / AI / NIAID NIH HHS / United States
RR 00044 / RR / NCRR NIH HHS / United States
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RR 02635 / RR / NCRR NIH HHS / United States