Association of Lifelong ART with Anti-Mullerian Hormone and Fecundability in African Women

About This Grant

PROJECT SUMMARY Antiretroviral treatment (ART) is now universal. In women living with HIV (WLHIV), ART reduces perinatal HIV transmission and improves maternal health. In sub-Saharan Africa, women are surviving healthier and longer in a setting where most of the global HIV infections have occurred. However, other aspects of the lifespan for these women need monitoring and further planning. Specifically, areas related to reproductive health, fertility expectations, aging, and pre-menopause/menopause have not been adequately examined in the African setting. Although ART is effective and safe, its long-term assessment should continue to examine potential interactions with reproductive hormones (RHs) that physiologically impact reproduction and other aspects of health. These reproductive health data are scarce in Africa among aging populations. It should be realized that ART is not limited to treatment of those living with HIV; it will soon encompass wider coverage through pre-exposure prophylaxis and long-acting regimens for women living without HIV. Therefore, a longitudinal assessment of the RHs that influence conception and their potential association with infecundity, premature menopause, and menstrual irregularity is an important, unique priority to address the evolving needs of WLHIV as they age. We propose a longitudinal study of the female anti- mullerian hormone (AMH), a marker of ovarian reserve and produced by the granulosa cells of the ovary, utilizing recently collected samples from WLHIV on lifelong ART in a cohort study called “PROMOTE” (a multi-country, observational study conducted at eight African sites during 2016-2021). In the proposed study, we will use laboratory samples and data from the Blantyre site in Malawi. We have robust data already collected on sociodemographic, sexual, and reproductive health (including use of hormonal contraceptives), and clinical (including viral load and CD4 cell counts) information from baseline and at follow-up visits every six months for approximately five years. We noted an interesting observation at study completion at the Blantyre site: 112 WLHIV on lifelong ART (41% of 273 who did not have a hysterectomy or tubal ligation) never became pregnant during follow-up, and 161 (59%) became pregnant at least once. This raises a question whether HIV/ART (or other related factors) is associated with infecundability. To investigate this observation further, we will measure AMH levels at baseline and at each follow-up visit. We will compare AMH values at baseline from the PROMOTE cohort to measurements obtained from a separate control group of non-pregnant, age-matched, women without HIV recruited from the same clinics in Blantyre, Malawi. The control group will include two groups of women using/not using HCs to allow evaluation of the impact of HCs use on AMH. These data will allow us to determine the association of lifelong ART with AMH and its impact on fecundity. This exploratory study could have high reward to the scientific community involved in reproductive health management.