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.
Highlights
Approximately 37.9 million people are living with HIV-1, with approximately two-thirds of infected individuals living in sub-Saharan Africa
Based on the quantitative viral outgrowth assay (QVOA), an assay widely accepted for measurement of reservoir size, we found that Ugandan women have a reduced frequency of resting CD4+ T cells (rCD4) containing replication-competent HIV-1 compared with their male peers
This was despite having similar frequencies of rCD4 containing HIV-1 DNA
Summary
Approximately 37.9 million people are living with HIV-1, with approximately two-thirds of infected individuals living in sub-Saharan Africa. HIV-1 remains incurable despite effective suppression of active viral replication by antiretroviral therapy (ART). This is owing to the persistence of a reservoir of stably integrated and replication-competent HIV-1 provirus, primarily in resting CD4+ T cells (rCD4), which leads to viral rebound rapidly after ART cessation [1]. This viral reservoir decays incredibly slowly, with a mean half-life of 44 months; people living with HIV-1 require lifetime use of ART [2, 3].
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