Background. Understanding HIV dynamics across the human body is important for cure efforts. This goal has been hampered by technical difficulties and the challenge to obtain fresh tissues. Methods. This observational study evaluated 6 persons with HIV (4 virally suppressed with antiretroviral therapy and 2 with rebound viremia after stopping therapy) who provided blood serially before death and their bodies for rapid autopsy. HIV reservoirs were characterized by digital droplet PCR and single genome amplification and sequencing of full-length (FL) envelope HIV. Phylogeographic methods reconstructed HIV spread and generalized linear models tested for viral factors associated with dispersal. Results. Across participants, HIV DNA levels varied from ~0 to 659 copies/106 cells (IQR:22.9-126.5). A total of 605 intact FL env sequences were recovered in antemortem blood cells and across 28 tissues (IQR:5-9). Sequence analysis showed: 1) emergence of large, identical, intact HIV RNA populations in blood after stopping therapy, which repopulated tissues throughout the body, 2) multiple sites acted as hubs for HIV dissemination but blood and lymphoid tissues were the main source, and 3) viral exchanges occurred within brain areas and across the blood brain barrier, and 4) migration was associated with low HIV divergence between sites and higher diversity at the recipient site. Conclusion. HIV reservoirs persist in all deep tissues, and blood is the main source of dispersal. This may explain why eliminating HIV susceptibility in circulating T cells via bone marrow transplants allowed some people with HIV to have therapy free remission, even though deeper tissue reservoirs were not targeted. Trial registration. Not applicable. Funding. National Institute of Health Grants (P01 AI31385, P30 AI036214, AI131971-01, AI120009AI036214,HD094646, AI027763, AI134295, AI68636).
Antoine Chaillon, Sara Gianella, Simon Dellicour, Stephen A. Rawlings, Timothy E. Schlub, Michelli Faria De Oliveira, Caroline Ignacio, Magali Porrachia, Bram Vrancken, Davey M. Smith