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.

Project Narrative We aim to quantify how traditional HIV therapy (ART) and antibodies against HIV (bnAbs) lose efficacy during treatment interruption in people with HIV, for bnAbs, distinguishing between antiviral and potential "vaccine"- like effects. The study will analyze ART levels in plasma, blood cells, and tissues as it relates to viral rebound and changes in reservoirs during ATI, and assess bnAb antiviral activity in human tonsil tissue cells. This research will guide the design of future HIV cure trials, providing essential insights into cure treatment efficacy with broader implications for HIV treatment and prevention.