The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals.

TitleThe setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1-infected individuals.
Publication TypeJournal Article
Year of Publication2012
AuthorsHogan CM, Degruttola V, Sun X, Fiscus SA, Del Rio C, C Hare B, Markowitz M, Connick E, Macatangay B, Tashima KT, Kallungal B, Camp R, Morton T, Daar ES, Little S
Corporate AuthorsA5217 Study Team
JournalJ Infect Dis
Volume205
Issue1
Pagination87-96
Date Published2012 Jan 1
ISSN1537-6613
KeywordsAdenine, Adult, Anti-HIV Agents, Deoxycytidine, Disease Progression, Drug Administration Schedule, Drug Combinations, Drug Therapy, Combination, Emtricitabine, Female, HIV Infections, HIV-1, Humans, Lopinavir, Male, Organophosphonates, Ritonavir, RNA, Viral, Tenofovir, Treatment Outcome, Viral Load
Abstract

BACKGROUND: The benefits of antiretroviral therapy during early human immunodeficiency virus type 1 (HIV-1) infection remain unproved.

METHODS: A5217 study team randomized patients within 6 months of HIV-1 seroconversion to receive either 36 weeks of antiretrovirals (immediate treatment [IT]) or no treatment (deferred treatment [DT]). Patients were to start or restart antiretroviral therapy if they met predefined criteria. The primary end point was a composite of requiring treatment or retreatment and the log(10) HIV-1 RNA level at week 72 (both groups) and 36 (DT group).

RESULTS: At the June 2009 Data Safety Monitoring Board (DSMB) review, 130 of 150 targeted participants had enrolled. Efficacy analysis included 79 individuals randomized ≥72 weeks previously. For the primary end point, the IT group at week 72 had a better outcome than the DT group at week 72 (P = .005) and the DT group at week 36 (P = .002). The differences were primarily due to the higher rate of progression to needing treatment in the DT group (50%) versus the IT (10%) group. The DSMB recommended stopping the study because further follow-up was unlikely to change these findings.

CONCLUSIONS: Progression to meeting criteria for antiretroviral initiation in the DT group occurred more frequently than anticipated, limiting the ability to evaluate virologic set point. Antiretrovirals during early HIV-1 infection modestly delayed the need for subsequent treatment.

CLINICAL TRIALS REGISTRATION: NCT00090779.

DOI10.1093/infdis/jir699
Alternate JournalJ. Infect. Dis.
PubMed ID22180621
PubMed Central IDPMC3242744
Grant List5-MO1 RR00044 / RR / NCRR NIH HHS / United States
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