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

J Infect Dis. 2012 Jan 1;205(1):87-96. doi: 10.1093/infdis/jir699. Epub 2011 Dec 15.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease Progression
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Emtricitabine
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Lopinavir / therapeutic use*
  • Male
  • Organophosphonates / therapeutic use*
  • RNA, Viral / blood
  • Ritonavir / therapeutic use*
  • Tenofovir
  • Treatment Outcome
  • Viral Load*

Substances

  • Anti-HIV Agents
  • Drug Combinations
  • Organophosphonates
  • RNA, Viral
  • lopinavir-ritonavir drug combination
  • Deoxycytidine
  • Lopinavir
  • Tenofovir
  • Emtricitabine
  • Adenine
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00090779

Grants and funding