Rapid clearance of inducible HIV-1 proviruses after initiation of antiretroviral therapy

Despite its efficacy, antiretroviral therapy (ART) is not curative, and HIV-1 rebound occurs whenever treatment is interrupted. The viral reservoir in latently infected cells is the source of the infection resurgence, making it crucial to understand when and how this reservoir is established so that it can be targeted more effectively. In this study, we evaluated the decay dynamics of proviral DNA in 40 ART-naive people initiating dolutegravir-based treatment and compared these dynamics to the decay kinetics of inducible proviruses, as measured using the VIP-SPOT assay. Intensive sampling during the first month, followed by regular sampling up to 48 weeks, enabled us to outline the biphasic decay dynamics of different fractions of the viral reservoir. Our results show that the first decay phase of inducible proviruses is significantly faster than that of total HIV-1 DNA (2.6 days versus 5.1 weeks), indicating that selective pressure on this specific fraction of proviruses is particularly effective during the first days after ART initiation. These findings suggest that therapeutic interventions aimed at impacting the viral reservoir by boosting the immune response targeting the inducible fraction should be implemented at the time of, or immediately before, treatment initiation.