Characterizing Antiviral Washout and Viral Rebound during Analytic Treatment Interruption Studies

Project Summary/Abstract Quantifying when antiviral activity of antiretroviral therapy (ART) or novel broadly neutralizing antibodies (bnAbs) wane in people with HIV during treatment interruption is critical to develop therapies to cure HIV. Further, in curative therapeutic trials, determining effects of bnAbs against virus as opposed to a potential immune-driven “vaccinal” effect, is essential to evaluating long-lasting post treatment efficacy. Here we propose to leverage existing data and technologies to quantify ART in plasma, cells in circulating blood, and tissue from an observation ART interruption study, to quantify how waning levels of ART alone are related to viral rebound and changes in reservoirs in the same samples (Aim 1). Then, we will quantify antiviral activity of bnAbs in human tonsil tissue cells and use this to inform the relative contribution of antiviral activity as opposed to another immune-mediated effect during a clinical intervention study using the same bnAb (Aim 2). These aims will provide essential knowledge surrounding viral rebound during ART interruption including optimal timing to assess therapeutic efficacy and determine if the postulated “vaccinal” effects of bnAbs exist. This work with inform design of future clinical trials for HIV cure but will also have broad implications for HIV treatment and prevention.