Virologic determinants of success after structured treatment interruptions of antiretrovirals in acute HIV-1 infection

J Acquir Immune Defic Syndr. 2008 Feb 1;47(2):140-47.

Abstract

Background: Latently infected resting memory CD4 T cells are thought to be the major reservoir that contributes to rebound viremia after cessation of antiretrovirals (ARVs). Commencing ARVs during primary HIV-1 infection (PHI) may limit the size of the latent pool and lead to improved control of viral replication during structured treatment interruption (STI).

Methods: Individuals with PHI (n = 59) were randomized to receive ARVs with or without hydroxyurea. After STI, a good response was defined as maintenance of HIV-1 RNA <5000 copies/mL for 24 weeks off therapy. In a detailed prospective virologic substudy (n = 19), integrated HIV-1 DNA, total HIV-1 DNA, and cell-associated HIV-1 unspliced (US) RNA were quantified using a real-time polymerase chain reaction assay.

Results: The plasma HIV-1 RNA 12 weeks after the initiation of ARVs was significantly lower in good responders (n = 7) compared with poor responders (n = 12) (P = 0.005). There were no significant differences between good and poor responders in integrated HIV-1 DNA, HIV-1 DNA, and HIV-1 US RNA. Integrated HIV-1 DNA before initiation of ARVs was strongly correlated with plasma HIV-1 RNA at week 12 (P = 0.006, r = 0.81).

Conclusion: HIV-1 RNA measured 12 weeks after initiation of ARV was the only virologic variable associated with viral rebound after treatment interruption in PHI.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • DNA, Viral / analysis
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • Humans
  • Hydroxyurea / therapeutic use*
  • RNA, Viral / blood
  • Treatment Outcome
  • United States
  • Viremia*
  • Virus Integration
  • Withholding Treatment*

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • RNA, Viral
  • Hydroxyurea