Near full-length HIV sequencing in multiple tissues collected post-mortem reveals shared clonal expansions across distinct tissue reservoirs during ART
HIV persists in blood and tissues during antiretroviral therapy (ART) but the relative contribution of different anatomical compartments to the viral reservoir in humans remains unknown. We perform an extensive characterization of HIV reservoirs in tissues collected from two men who donated their bodies to HIV cure research and who had been on suppressive ART for years. HIV DNA and HIV transcripts are detected in all tissues, with large variations across anatomical compartments and between participants. A total of 441 near full-length (NFL) proviral sequences were obtained. Intact HIV genomes represent 2% and 25% of all proviruses in the two participants, and are mainly detected in secondary lymphoid organs, with the spleen and mediastinal lymph nodes harboring intact viral genomes in both individuals. Multiple copies of identical HIV genomes are found in all tissues, indicating that clonal expansions are not only common in blood but also in anatomical sites. The majority (>85%) of these expanded clones are shared across multiple tissues. These findings suggest that infected cells harboring either intact or defective proviruses expand, migrate, and possibly circulate between anatomical sites.