HIV persists throughout deep tissues with repopulation from multiple anatomical sources
Open accessAbstract
BACKGROUNDUnderstanding HIV dynamics across the human body is important for cure efforts. This goal has been hampered by technical difficulties and the challenge of obtaining fresh tissues.METHODSThis observational study evaluated 6 individuals with HIV (n = 4 with viral suppression using antiretroviral [ART] therapy; n = 2 with rebound viremia after stopping ART), who provided serial blood samples before death and their bodies for rapid autopsy. HIV reservoirs were characterized by digital droplet PCR, single-genome amplification, and sequencing of full-length (FL) envelope HIV. Phylogeographic methods were used to reconstruct HIV spread, and generalized linear models were tested for viral factors associated with dispersal.RESULTSAcross participants, HIV DNA levels varied from approximately 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 (a) the emergence of large, identical, intact HIV RNA populations in blood after cessation of therapy, which repopulated tissues throughout the body; (b) that multiple sites acted as hubs for HIV dissemination but that blood and lymphoid tissues were the main source; (c) that viral exchanges occurred within brain areas and across the blood-brain barrier; and (d) that migration was associated with low HIV divergence between sites and greater diversity at the recipient site.CONCLUSIONHIV reservoirs persisted in all deep tissues, and blood was the main source of dispersal. This may explain why eliminating HIV susceptibility in circulating T cells via bone marrow transplants allowed some individuals with HIV to experience therapy-free remission, even though deeper tissue reservoirs were not targeted.TRIAL REGISTRATIONNot applicable.FUNDINGNIH grants P01 AI31385, P30 AI036214, AI131971-01, AI120009AI036214, HD094646, AI027763, AI134295, and AI68636.
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Infected cells are found mainly in various distant organs, including lymph nodes, gut, brain, and others.
“Therefore, infected cells are found mainly in various distant organs, including lymph nodes, gut, brain, and others. 13,14”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [14]
The Discussion reports HIV-infected cells in the CNS and several other organs, and the study found intact HIV sequences across 28 sampled anatomical compartments, including lymph nodes and gut. It does not establish that infected cells are found mainly in distant organs; the Results identify blood and lymphoid tissues as the main sources of viral dissemination. (LLM, conf=0.83)
Experimental — accuracy not yet measuredStudies have suggested a close genetic relatedness of recovered viruses, suggesting that viral re- and deactivation and organ homing are interconnected for different body compartments.
“Studies have suggested a close genetic relatedness of recovered viruses, suggesting that viral reand deactivation and organ homing are interconnected for different body compartments. 13,14,44,45”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [14]
The discussion (page not specified in the index) reports nearly identical viruses in blood and multiple tissues after treatment interruption and suggests that rebounding virus replenished tissue reservoirs. The “Viral dispersal and repopulation” section also documents movement between anatomical sites. The paper does not establish the claimed link between viral deactivation and organ homing. (LLM, conf=0.82)
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“Studies have suggested a close genetic relatedness of recovered viruses, suggesting that viral re- and deactivation and organ homing are interconnected for different body compartments.(13,14,44,45) Further studies will now focus on the viral dynamics over time by longitudinally studying the clonal evolution of single…”
BackgroundMethod
- Authors
- Chaillon, A., Gianella, S., Dellicour, S., Rawlings, S. A., Schlub, T. E., De Oliveira, M. F., Ignacio, C., Porrachia, M., Vrancken, B., & Smith, D. M.
- Affiliations
- University of California San Diego (US)
- Université Libre de Bruxelles (BE)
- The University of Sydney (AU)
- KU Leuven (BE)
- Corresponding author
- Chaillon, Antoine
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2020-02-24
- Volume
- 130
- Issue
- 4
- Pages
- 1699-1712
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC7108926
- OpenAlex
- W2999054912
- Cited by
- 250
- References
- 4
- Citations by year
- 2026: 36 · 2025: 35 · 2024: 28 · 2023: 41 · 2022: 35 · 2021: 43 · 2020: 27 · 2019: 4 · 2018: 1
- FWCI
- 19.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- Funders
- National Institute of Health, United States (AI131971-01,AI036214,HD094646,AI027763,AI134295,AI68636,AI036214)
- University of San Diego Center for AIDS Research (NA)
- Veterans Medical Research Foundation (NA)
- Fonds voor Wetenschappelijk Onderzoek (NA)
- Fonds National de la Recherche Scientifique (NA)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- HIV reservoir, HIV rebound, HIV cure, blood-brain barrier, antiretroviral therapy, bone marrow transplantation, lymphoid tissue
- MeSH terms
- Aged, DNA, Viral, Female, Humans, Male, Middle Aged, Organ Specificity, RNA, Viral, HIV-1, HIV Infections, Viral Load, Anti-Retroviral Agents
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