Background A key research priority for developing a human immunodeficiency virus (HIV) cure strategy is to define the viral dynamics and biomarkers associated with sustained posttreatment control. The ability to predict the likelihood of sustained posttreatment control or noncontrol could minimize the time off antiretroviral therapy (ART) for those destined to be controllers and anticipate longer periods off ART for those destined to be controllers.Methods Mathematical modeling and machine learning were used to characterize virologic predictors of long-term virologic control, using viral kinetics data from several studies in which participants interrupted ART. Predictors of post-ART outcomes were characterized using data accumulated from the time of treatment interruption, replicating real-time data collection in a clinical study, and classifying outcomes as either posttreatment control (plasma viremia, <= 400 copies/mL at 2 of 3 time points for >= 24 weeks) or noncontrol.Results Potential predictors of virologic control were the time to rebound, the rate of initial rebound, and the peak plasma viremia. We found that people destined to be noncontrollers could be identified within 3 weeks of rebound (prediction scores: accuracy, 80%; sensitivity, 82%; specificity, 71%).Conclusions Given the widespread use of analytic treatment interruption in cure-related trials, these predictors may be useful to increase the safety of analytic treatment interruption through early identification of people who are unlikely to become posttreatment controllers.
[1]Gilead Sci, Biol Dept, Foster City, CA 94404 USA.
[2]Univ Calif San Diego, Dept Med, La Jolla, CA USA.
[3]Ragon Inst Mass Gen MIT & Harvard, Cambridge, MA USA.
[4]Howard Hughes Med Inst, Chevy Chase, MD USA.
[5]Glen Site Res Inst, Div Hematol, Montreal, PQ, Canada.
[6]Glen Site Res Inst, McGill Univ Hlth Ctr, Chron Viral Illness Serv, Montreal, PQ, Canada.
[7]Univ Calif San Francisco, Osher Ctr Integrat Hlth, San Francisco, CA USA.
[8]NIH, Lab Immunoregulat, Bethesda, MD USA.
[9]Harvard Med Sch, Brigham & Womens Hosp, Div Infect Dis, Boston, MA USA.
[10]Univ Calif San Francisco, Div HIV Infect Dis & Global Med, San Francisco, CA 94110 USA.
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