title: The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aBrigham and Women's Hospital, Harvard Medical School bHarvard T. H. Chan School of Public Health, Boston, Massachusetts cUniversity of Pittsburgh, Pittsburgh, Pennsylvania dCase Western Reserve University, Cleveland eOhio State University, Columbus, Ohio fMassachusetts General Hospital and Ragon Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Li
authors.forename: Behzad
authors.initials: B
authors.lastname: Etemad
authors.forename: Hayat
authors.initials: H
authors.lastname: Ahmed
authors.forename: Evgenia
authors.initials: E
authors.lastname: Aga
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Michael
authors.initials: M
authors.lastname: Para
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D005260:Female; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D012008:Recurrence; D013997:Time Factors; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents