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Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda
JCI Insight (2020)
  • Jessica Prodger, Western University
  • Adam A. Capoferri
  • Katherine Yu
  • Jun Lai
  • Steven J. Reynolds, Johns Hopkins University
  • Jingo Kasule
Abstract
HIV-1 infection remains incurable owing to the persistence of a viral reservoir that harbors integrated provirus within host cellular DNA. Increasing evidence links sex-based differences in HIV-1 immune responses and pathogenesis; however, little is known about differences in HIV-1 infection persistence. Here, we quantified persistent HIV-1 infection in 90 adults on suppressive antiretroviral therapy in Rakai, Uganda (57 female patients). Total HIV-1 DNA was quantified by PCR, and replication-competent provirus by quantitative viral outgrowth assay (QVOA). Immune phenotyping of T cell subsets and plasma biomarkers was also performed. We found that whereas both sexes had similar total HIV DNA levels, female patients had significantly fewer resting CD4+ T cells harboring replication-competent virus, as measured by viral outgrowth in the QVOA. Factors associated with viral outgrowth differed by sex; notably, frequency of programmed cell death 1 (PD1+) CD4+ T cells correlated with reservoir size in male but not female patients. The sex-based differences in HIV-1 persistence observed in this cohort warrant additional research, especially given the widespread use of the QVOA to assess reservoir size and current explorations of PD1 agonists in cure protocols. Efforts should be made to power future cure studies to assess outcomes in both male and female patients.
Keywords
  • Chemokines,
  • Sex hormones,
  • T cells,
  • AIDS/HIV
Publication Date
Summer July 23, 2020
DOI
10.1172/jci.insight.139287
Citation Information
Jessica Prodger, Adam A. Capoferri, Katherine Yu, Jun Lai, et al.. "Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda" JCI Insight (2020)
Available at: http://works.bepress.com/jessica-prodger/6/