The brain as an HIV reservoir: Recent findings using autopsy tissues from people with HIV
12 affiliations
- 1Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
- 2Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
- 3The Emmes Company LLC, Rockville, Maryland, United States of America
- 4Dana-Farber Cancer Institute and Harvard Medical School, Boston, Maryland, United States of America
- 5ATRACT Research Centre, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Melbourne, Victoria, Australia
- 6AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
- 7Department of Internal Medicine, University of California, San Diego, La Jolla, California, United States of America
- 8Department of Psychiatry, University of California, San Diego, La Jolla, California, United States of America
- 9Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, United States of America
- 10Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America
- 11Department of Neurology, University of California, Los Angeles, Los Angeles, California, United States of America
- 12Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America
Abstract
HIV persistence within anatomical reservoirs remains the primary barrier to achieving an HIV cure. While antiretroviral therapy effectively suppresses plasma viremia, it does not eliminate integrated proviral genomes that persist in long-lived cellular compartments. The central nervous system (CNS) is a clinically important HIV reservoir, characterized by immune privilege and the persistence of tissue-resident infection despite effective antiretroviral therapy (ART). Evidence from postmortem studies reveals that HIV DNA, RNA, and even intact replication-competent proviruses remain detectable in brain tissue from virally suppressed people with HIV. Evidence derived primarily from in situ approaches and viable-cell studies supports myeloid-lineage reservoirs, particularly microglia and CNS-associated macrophages, as key cellular sources of persistence, while the extent and biological relevance of astrocyte infection remains debated. These reservoirs exhibit transcriptional activity and are associated with chronic neuroinflammation, which may contribute to HIV-associated neurocognitive disorders, despite systemic viral suppression. Here, we synthesize recent findings from autopsy brain studies, including work enabled by major biorepositories, such as the National NeuroHIV Tissue Consortium and rapid-autopsy programs, including the Last Gift, both of which are essential for studying HIV reservoirs in the CNS. We summarize methodologies for detecting and characterizing HIV in brain tissue, highlight heterogeneous patterns of regional distribution and compartmentalization, and review emerging links between CNS persistence and neuroinflammation. We conclude with priorities for harmonized tissue processing, multi-modal single-cell and spatial profiling, and coordinated cross-cohort analyses to clarify the contribution of CNS reservoirs to neuroHIV pathogenesis and systemic rebound.
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BibTeX
@article{dave2026brain,
title = {{The brain as an HIV reservoir: Recent findings using autopsy tissues from people with HIV}},
author = {Rajnish S. Dave and Ayo A. Oludipe and Elizabeth C. Pasipanodya and Seth J. Sherman and Steffanie H Wilson and Dana H. Gabuzda and Melissa J. Churchill and Thomas A. Angelovich and Robert J. Gorelick and Sara Gianella and Antoine Chaillon and Jerel Adam Fields and Susan Morgello and Benjamin B. Gelman and David J. Moore and Elyse J. Singer and Beau M. Ances and Howard S. Fox},
journal = {PLoS Pathogens},
year = {2026},
month = jul,
doi = {10.1371/journal.ppat.1014446},
url = {https://doi.org/10.1371/journal.ppat.1014446},
note = {Public domain},
}
RIS
TY - JOUR
TI - The brain as an HIV reservoir: Recent findings using autopsy tissues from people with HIV
AU - Rajnish S. Dave
AU - Ayo A. Oludipe
AU - Elizabeth C. Pasipanodya
AU - Seth J. Sherman
AU - Steffanie H Wilson
AU - Dana H. Gabuzda
AU - Melissa J. Churchill
AU - Thomas A. Angelovich
AU - Robert J. Gorelick
AU - Sara Gianella
AU - Antoine Chaillon
AU - Jerel Adam Fields
AU - Susan Morgello
AU - Benjamin B. Gelman
AU - David J. Moore
AU - Elyse J. Singer
AU - Beau M. Ances
AU - Howard S. Fox
PY - 2026
DA - 2026/07/29
JO - PLoS Pathogens
DO - 10.1371/journal.ppat.1014446
UR - https://doi.org/10.1371/journal.ppat.1014446
AB - HIV persistence within anatomical reservoirs remains the primary barrier to achieving an HIV cure. While antiretroviral therapy effectively suppresses plasma viremia, it does not eliminate integrated proviral genomes that persist in long-lived cellular compartments. The central nervous system (CNS) is a clinically important HIV reservoir, characterized by immune privilege and the persistence of tissue-resident infection despite effective antiretroviral therapy (ART). Evidence from postmortem studies reveals that HIV DNA, RNA, and even intact replication-competent proviruses remain detectable in brain tissue from virally suppressed people with HIV. Evidence derived primarily from in situ approaches and viable-cell studies supports myeloid-lineage reservoirs, particularly microglia and CNS-associated macrophages, as key cellular sources of persistence, while the extent and biological relevance of astrocyte infection remains debated. These reservoirs exhibit transcriptional activity and are associated with chronic neuroinflammation, which may contribute to HIV-associated neurocognitive disorders, despite systemic viral suppression. Here, we synthesize recent findings from autopsy brain studies, including work enabled by major biorepositories, such as the National NeuroHIV Tissue Consortium and rapid-autopsy programs, including the Last Gift, both of which are essential for studying HIV reservoirs in the CNS. We summarize methodologies for detecting and characterizing HIV in brain tissue, highlight heterogeneous patterns of regional distribution and compartmentalization, and review emerging links between CNS persistence and neuroinflammation. We conclude with priorities for harmonized tissue processing, multi-modal single-cell and spatial profiling, and coordinated cross-cohort analyses to clarify the contribution of CNS reservoirs to neuroHIV pathogenesis and systemic rebound.
SN - 1553-7366
SN - 1553-7374
ER -