Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda

Jessica L. Prodger, Adam A. Capoferri, Katherine Yu, Jun Lai, Steven J. Reynolds, Jingo Kasule, Taddeo Kityamuweesi, Paul Buule, David Serwadda, Kyungyoon J. Kwon, Katherine Schlusser, Craig Martens, Eileen Scully, Yun Hee Choi, Andrew D. Redd, Thomas C. Quinn

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere139287
JournalJCI Insight
Volume5
Issue number14
DOIs
StatePublished - Jun 23 2020

ASJC Scopus subject areas

  • Medicine(all)

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