Evaluation of HIV-1 reservoir size and broadly neutralizing antibodies (bNAb) susceptibility in acute ART treated individuals.

OBJECTIVE Persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during acute HIV infection can limit the size and diversity of the reservoir. In depth characterization of the reservoir in individuals who initiate ART during acute infection will be critical for clinical trial design and cure strategies. METHODS Four cohorts with participants who initiated ART during acute infection or during chronic infection were enrolled in a cross-sectional, non-interventional study. Viral reservoir was evaluated by the Intact Proviral DNA Assay (IPDA), the Total HIV DNA assay (THDA) and the Quantitative Viral Outgrowth Assay (QVOA). Viral diversity and susceptibility to V3-glycan bNAbs were determined by genotyping of the viral envelope gene. RESULTS Participants who initiated ART during the acute Fiebig I-IV stages had lower level of total HIV DNA than participants who initiated ART during chronic infection whereas no difference was observed in intact HIV DNA or outgrowth virus. Participants who initiated ART during Fiebig I-IV also had lower viral diversity and appeared to have higher susceptibility to bNAbs than participants initiating ART during chronic infection. CONCLUSIONS Individuals initiating ART during Fiebig I-IV had small viral reservoirs, low viral diversity and high susceptibility to bNAbs, and would be an optimal target population for proof of concept HIV cure trials.