Sex Differences in Human Immunodeficiency Virus Persistence and Reservoir Size During Aging

Abstract Background Sex differences in human immunodeficiency virus (HIV) reservoir dynamics remain underexplored. Methods Longitudinal samples from virally suppressed midlife women (n = 59, median age 45 years) and age-matched men (n = 31) were analyzed retrospectively. At each time point, we measured sex hormones (by means of enzyme-linked immunosorbent assay) and cellular HIV DNA and RNA (by means of digital droplet polymerase chain reaction). Number of inducible HIV RNA+ cells, which provides an upper estimate of the replication-competent reservoir, was quantified longitudinally in a different subset of 14 women, across well-defined reproductive stages. Mixed-effects models included normalized reservoir outcomes and sex, time since antiretroviral therapy (ART) initiation, and the sex-by-time interaction as predictors. Results At ART initiation, women and men had median (interquartile range [IQR]) CD4+ T-cell counts of 204/μL (83–306/μL) versus 238/μL (120–284/μL), respectively; median ages of 45 (42–48) versus 47 (43–51) years; and median follow-up times of 79.2/μL (60.5–121.1/μL) versus 66.2/μL (43.2–80.6/μL) months. We observed a significant decline of total HIV DNA over time in both men and women (P