HIV Rebound Kinetics and CD4+ T-Cell Loss after Treatment Interruption: A Pooled Analysis of Six AIDS Clinical Trials Group (ACTG) Studies
Background: Strategies for antiretroviral therapy (ART)-free HIV remission (“functional cure”) will ultimately require validation through analytic treatment interruption (ATI) studies. The risks associated with treatment interruption may be minimized using an intensively monitored antiretroviral pause (MAP) strategy with the timing of viral rebound as the primary outcome instead of viral load (VL) set point, and that restarts ART once a viral load threshold is reached. We performed a pooled analysis of ACTG ATI studies to evaluate the timing of HIV rebound and CD4+ cell loss, and to compare the ATI strategy to a hypothetical MAP strategy.
Methods: Participants of 6 ACTG ATI studies were included if they were on suppressive ART (<50 HIV RNA cp/mL) and received no immunologic interventions. Two primary definitions of viral rebound were assessed (confirmed VL ≥200 cp/mL or single VL ≥1,000 cp/mL); the analysis was stratified by timing of ART initiation and screening CD4+ count.
Results: A total of 263 participants were included, of whom 182, 38, and 43 participants initiated ART during chronic, acute, and recent HIV infection, respectively. While the majority of participants had detectable VL by week 4, a subset of participants was found to have more durable viral suppression (Fig 1). At week 12, a smaller proportion of participants treated during chronic infection maintained HIV RNA <200 cp/mL (chronic vs. acute vs. recent: 3% vs. 11% vs. 14%, P<0.01 Fishers exact test). CD4+ counts were significantly higher at the time of detectable VL (confirmed VL≥200 cp/mL or single VL≥1,000 cp/mL) compared to the end of a 12-16 week ATI (Fig 2). There were no significant differences in CD4+ cell loss stratified by timing of ART initiation or screening CD4+ count.
Conclusion: Although most HIV+ patients have viral rebound within 4-8 weeks of stopping ART, a subset maintained drug-free remission for longer periods of time. Participants treated during acute/recent HIV infection were more likely to maintain virologic suppression after treatment interruption. Compared with the traditional ATI approach, a MAP strategy is associated with smaller declines in CD4+ counts. Future studies should assess virologic and immunologic determinants of delayed HIV rebound using a MAP strategy.
R. Bosch, None
J. Mellors, University of Pittsburgh: Employee, Salary
Brigham Women's Hospital, Inc.: Grant Investigator, Research grant
NIH: Grant Investigator, Research grant
Gilead Sciences: Scientific Advisor, Consulting fee
RFS Pharma: Stock Options, Value uncertain
D. Kuritzkes, None
M. Para, None
R. Gandhi, None