Sex differences in HIV Persistence and Reservoir Size during Aging.

BACKGROUND Sex differences in HIV reservoir dynamics remain under-explored. METHODS Longitudinal samples from virally suppressed midlife women (N=59) and age-matched men (N=31) were analyzed retrospectively. At each time point, we measured sex hormones (by ELISA), cellular HIV DNA and RNA (by digital droplet PCR). Number of inducible HIV RNA + cells, which provides an upper estimate of replication-competent reservoir, was quantified longitudinally on a different subset of 14 women, across well-defined reproductive stages. Mixed-effects models included normalized reservoir outcomes and sex, time since ART initiation, and the sex-by-time interaction as predictors. RESULTS At ART initiation, women and men had a median (IQR) CD4 + of 219 (82,324) cells/µl versus 248 (120, 290), median age (IQR) of 45 (42,48) versus 47 (43,51), and median follow up (IQR) of 93 (76,132) versus 74 (52,93) months. We observed a significant decline of total HIV DNA over time in both men and women (p<0.01). However, the rate of change significantly differed between sexes (p<0.01), with women having a significantly slower rate of decline as compared to men, more pronounced with age. By contrast, the levels of inducible HIV RNA increased incrementally over time in women during reproductive aging (<0.01). CONCLUSIONS In contrast to men, where the HIV reservoir steadily declines with aging, the HIV reservoir in women is more dynamic. Total HIV DNA (including intact and defective genomes) declines more slowly in women than in men, while the inducible HIV RNA + reservoir, which is highly enriched in replication competent virus, increases in women after menopause.