HIV Reservoir Dynamics and Immune Responses Across the Female Reproductive Life Span

About This Grant

Summary Efforts towards an HIV cure have elucidated the marked variation in the HIV reservoir and the immune responses between different individuals. Sex has emerged as a factor that is associated with differences across the spectrum of HIV from acquisition through pathogenesis and HIV reservoir dynamics. Although the mechanisms are incompletely defined, the sex steroid hormone 17β-estradiol has been shown to interact with HIV replication and maintenance of latency. Levels of this hormone vary dramatically over the lifespan, introducing periods of potential reservoir disruption that are unique to women. In addition, natural aging has sex-specific features, which may be partially linked to sex steroid hormone exposure, and this has intersections with HIV reservoir maintenance and immunity. Despite these data, there is a marked underrepresentation of women in studies relevant to HIV cure. This is in part due to the limited number of cure studies in Africa where the majority of women living with HIV reside; this has also meant that the majority of virologic assays have not been developed for non-subtype B viruses. In this proposal, we will address the knowledge gaps around sex-specific features of HIV reservoir with specific attention to aging across the reproductive lifespan in a cohort of Ugandans living with HIV. We will accomplish this with three specific aims: 1. Analyze the impact of pregnancy on HIV reservoir and immunity 2. Assess HIV reservoir and immunophenotype across the menopausal transition in comparison to chronologically age-matched men 3. Estimate epigenetic age in women and men living with HIV and assess for relationships with sex and HIV reservoir activity. We have assembled a multidisciplinary team, led by co-Principal Investigators Dr. Eileen Scully (Johns Hopkins University) and Dr. Ronald Galiwango (Rakai Health Sciences Program), who together have the expertise and infrastructure to recruit participants and perform the advanced analyses to accomplish these aims. The study will substantively advance the understanding of the non-subtype B reservoir in women across the reproductive lifespan and the intersections between sex, reservoir and aging with multiple potential implications for curative efforts.