The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption

AIDS. 2016 Jan 28;30(3):343-53. doi: 10.1097/QAD.0000000000000953.


Objectives: Therapies to achieve sustained antiretroviral therapy-free HIV remission will require validation in analytic treatment interruption (ATI) trials. Identifying biomarkers that predict time to viral rebound could accelerate the development of such therapeutics.

Design: A pooled analysis of participants from six AIDS Clinical Trials Group ATI studies to identify predictors of viral rebound.

Methods: Cell-associated DNA (CA-DNA) and CA-RNA were quantified in pre-ATI peripheral blood mononuclear cell samples, and residual plasma viremia was measured using the single-copy assay.

Results: Participants who initiated antiretroviral therapy (ART) during acute/early HIV infection and those on a non-nucleoside reverse transcriptase inhibitor-containing regimen had significantly delayed viral rebound. Participants who initiated ART during acute/early infection had lower levels of pre-ATI CA-RNA (acute/early vs. chronic-treated: median <92 vs. 156 HIV-1 RNA copies/10 CD4 cells, P < 0.01). Higher pre-ATI CA-RNA levels were significantly associated with shorter time to viral rebound (≤4 vs. 5-8 vs. >8 weeks: median 182 vs. 107 vs. <92 HIV-1 RNA copies/10 CD4 cells, Kruskal-Wallis P < 0.01). The proportion of participants with detectable plasma residual viremia prior to ATI was significantly higher among those with shorter time to viral rebound.

Conclusion: Higher levels of HIV expression while on ART are associated with shorter time to HIV rebound after treatment interruption. Quantification of the active HIV reservoir may provide a biomarker of efficacy for therapies that aim to achieve ART-free HIV remission.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Clinical Trials as Topic
  • Female
  • HIV Infections / virology*
  • HIV-1 / isolation & purification*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Plasma / virology
  • Recurrence
  • Time Factors
  • Viral Load*
  • Withholding Treatment*


  • Anti-HIV Agents