Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection

Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here show that early ART commencement is frequently associated with accelerated and efficient selection of genome-intact HIV-1 proviruses in repressive chromatin locations during the first year after treatment initiation. This selection process was unaffected by vaccine-induced HIV-1-specific T cell responses. Single-cell proteogenomic profiling demonstrated that cells harboring intact HIV-1 displayed a discrete phenotypic signature of immune selection by innate immune responses, characterized by a slight but significant upregulation of HLA-C, HLA-G, the IL-10 receptor, and other markers involved in innate immune regulation. Together, these results suggest an accelerated immune selection of viral reservoir cells during early-treated HIV-1 infection that seems at least partially driven by innate immune responses.

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Publication Details

Journal
The Journal of Experimental Medicine
Published
2024-10-28
DOI
https://doi.org/10.1084/jem.20241091
Citations
10
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
2.94

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article

Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection

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10 citations
The Journal of Experimental Medicine
HIV Research and Treatment
2.94
article

Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection

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article en
10 citations

Abstract

Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here show that early ART commencement is frequently associated with accelerated and efficient selection of genome-intact HIV-1 proviruses in repressive chromatin locations during the first year after treatment initiation. This selection process was unaffected by vaccine-induced HIV-1-specific T cell responses. Single-cell proteogenomic profiling demonstrated that cells harboring intact HIV-1 displayed a discrete phenotypic signature of immune selection by innate immune responses, characterized by a slight but significant upregulation of HLA-C, HLA-G, the IL-10 receptor, and other markers involved in innate immune regulation. Together, these results suggest an accelerated immune selection of viral reservoir cells during early-treated HIV-1 infection that seems at least partially driven by innate immune responses.

The Journal of Experimental MedicineVol. 221(11)
Brigham and Women's Hospital (US), Ragon Institute of MGH, MIT and Harvard (US), University of Oxford (GB), NIHR Imperial Biomedical Research Centre (GB)
Bill and Melinda Gates Foundation, amfAR, The Foundation for AIDS Research, National Institutes of Health, Medical Research Council
Good health and well-being
Openalex Percentile: Top 9%
HIV Research and Treatment
2.94
DOIOpen Access PDFOpenAlex
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