HIV reservoir dynamics according to the timing of antiretroviral therapy initiation or modification

• A successful dolutegravir-based regimen can reduce levels of total HIV DNA in viremic individuals, although the extent of this reduction varies. • A successful dolutegravir-based regimen can reduce levels of residual immune activation in viremic individuals, although the extent of this reduction varies. • A successful dolutegravir-based regimen, when used as a switching regimen, has no impact on HIV reservoir nor inflammation. HIV reservoir is the main barrier to HIV cure but its size dynamics on antiretroviral therapy (ART) in various clinical settings is poorly characterized. Responders to a dolutegravir-based regimen (DBR) enrolled in the DRONE study were analyzed for longitudinal total HIV DNA and immune activation biomarkers (sCD14, sCD163, IL-6, IP-10). Overall, 169 participants were allocated to various groups: ART-naive acute infections (AI, n = 20) or chronic infections (CI, n = 21), and ART-treated individuals in virological success (VS, n = 116) or failure (VF, n = 12). HIV DNA significantly decreased at W48 of successful DBR in the AI (median: −1.3 log 10 copies/million PBMCs), CI (−0.6), and VF (−0.5) groups, but not in the VS group. Activation biomarkers decreased on DBR only for individuals with ongoing HIV replication at baseline. Successful DBR was associated with rapid HIV DNA decline in ART-naive and ART-failing individuals but not in the context of ART switch.