Early Viral Dynamics Predict Human Immunodeficiency Virus Posttreatment Control After Analytic Treatment Interruption

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.

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.

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%).

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.