Predictors of SIV recrudescence following antiretroviral treatment interruption

Elife. 2019 Oct 25:8:e49022. doi: 10.7554/eLife.49022.

Abstract

There is currently a need for proxy measures of the HIV rebound competent reservoir (RCR) that can predict viral rebound after combined antiretroviral treatment (cART) interruption. In this study, macaques infected with a barcoded SIVmac239 virus received cART beginning between 4- and 27 days post-infection, leading to the establishment of different levels of viral dissemination and persistence. Later treatment initiation led to higher SIV DNA levels maintained during treatment, which was significantly associated with an increased frequency of SIV reactivation and production of progeny capable of causing rebound viremia following treatment interruption. However, a 100-fold increase in SIV DNA in PBMCs was associated with only a 2-fold increase in the frequency of reactivation. These data suggest that the RCR can be established soon after infection, and that a large fraction of persistent viral DNA that accumulates after this time makes relatively little contribution to viral rebound.

Keywords: HIV; immunity; infectious disease; latency; microbiology; virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Retroviral Agents / therapeutic use*
  • DNA, Viral / genetics*
  • DNA, Viral / metabolism
  • Leukocytes, Mononuclear / pathology
  • Leukocytes, Mononuclear / virology*
  • Macaca mulatta
  • Male
  • Prognosis
  • Recurrence
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / drug effects*
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / growth & development
  • Simian Immunodeficiency Virus / pathogenicity
  • Time-to-Treatment / statistics & numerical data
  • Treatment Outcome
  • Viral Load
  • Virus Activation*
  • Virus Replication

Substances

  • Anti-Retroviral Agents
  • DNA, Viral