Evaluation of Archival HIV DNA in Brain and Lymphoid Tissues
Michelli F. Oliveira, Alec Pankow, Thomas Vollbrecht, Nikesh M. Kumar, Gemma Cabalero, Caroline Ignacio, Mitchell Zhao, Andrej Vitomirov, Ben Gouaux, Masato Nakawawa, Ben Murrell, Ronald J. Ellis, Sara Gianella
Abstract
HIV infection of the brain is associated with adverse neuropsychiatric outcomes, despite efficient antiretroviral treatment. HIV may persist in reservoirs in the brain and other tissues, which can seed virus replication if treatment is interrupted, representing a major challenge to cure HIV. We evaluated reservoirs and genetic features in postmortem brain and lymphoid tissues from people with HIV who passed away during suppressed HIV replication. We found a differential distribution of HIV reservoirs across brain regions which was lower than that in lymphoid tissues. We observed that most HIV reservoirs in tissues had intact envelope sequences, suggesting they could potentially generate replicative viruses. We found that women had higher HIV reservoir levels in brain and lymphoid tissues than men, suggesting possible sex-based mechanisms of maintenance of HIV reservoirs in tissues, warranting further investigation. Characterizing the archival HIV DNA in tissues is important to inform future HIV cure strategies.