HIV-1 virome profiling using HIV-PULSE to guide therapeutic and curative interventions

<h4>Background</h4>The persistent HIV-1 reservoir remains a major barrier to curing HIV-1, underscoring the need for a detailed understanding of its composition to inform targeted interventions.<h4>Methods</h4>Here, we apply the HIV Proviral Unique molecular identifier-mediated Long-read Sequencing (HIV-PULSE) assay to characterise the viral reservoir in 90 individuals on suppressive antiretroviral therapy. By generating near full-length proviral sequences, HIV-PULSE enables multiple layers of in silico analyses across the HIV-1 genome.<h4>Findings</h4>These data support the construction of participant-specific HIV virome profiles, integrating assessments of proviral intactness, tropism, genetic diversity, archived drug resistance mutations and susceptibility to selected immune-based therapies (broadly neutralising antibodies and HIV-specific immune-mobilising monoclonal T cell receptor therapy IMC-M113V).<h4>Interpretation</h4>Our findings demonstrate that HIV-PULSE provides a comprehensive platform for individualised reservoir profiling, advancing future treatment perspectives and efforts towards an HIV-1 cure.<h4>Funding</h4>This research is part of the 2000HIV study, supported by ViiV Healthcare.