Determining Bone Loss and Bone Mineral Density Recovery Following Repeat Pregnancy/Lactation Among HIV Women on ART

Johns Hopkins University, Baltimore MD

Investigators

Abstract

PROJECT SUMMARY / ABSTRACT Among HIV-infected women, the longer-term impact that lifetime antiretroviral therapy (ART) with repeat pregnancy followed by breastfeeding has on maternal health outcomes including bone mineral density (BMD), in particular, remains unknown. Findings from the PROMISE 1077BF trial indicated that BMD significantly decreased among asymptomatic HIV-infected mothers randomized to receive ART during extended breastfeeding compared to mothers whose infants were randomized to receive nevirapine prophylaxis during breastfeeding. Breastfeeding was also associated with transient decreases in BMD but was usually followed by BMD recovery. Lactating women with HIV taking tenofovir-based ART had altered milk mineral composition (i.e. calcium) when compared to women without HIV. These initial results from the PROMISE trial reporting BMD decreases with ART during breastfeeding and metabolic differences for lactating mothers on ART from the Gumba study raise concerns about potentially increased risk of early osteopenia or osteoporosis compared to mothers are not HIV-infected and not exposed to lifetime ART. To better understand this relationship, the Maternal Bone Health Study (MBHS) is a prospective longitudinal follow up study being conducted to assess BMD changes with repeat pregnancy and extended breastfeeding among HIV-infected mothers from the PROMISE trial who are now enrolled as participants in the PROMOTE cohort. This observational MBHS is being conducted at clinical research sites in Blantyre, Malawi and Kampala, Uganda to explore factors which may affect bone health and both loss and recovery patterns of BMD for HIV-infected women on lifetime ART. The Specific Aims of the MBHS are: (1) to gather baseline BMD data at entry into PROMOTE and to compare to prior bone density scans, DXA measures, from PROMISE in order to assess changes clinical risk factors for low BMD in HIV-infected women and (2) to determine BMD loss and recovery patterns in from bone biomarker changes during a 36-month post-delivery period among HIV-infected women who have a repeat pregnancy during PROMOTE follow up with results being compared to age group- and parity-matched HIV-negative pregnant women at each site. Lastly, the MBHS will aim (3) to compare BMD and bone biomarker findings with PROMOTE mothers matched for age group and parity by site who do not conceive during 36 months of follow-up. These comparisons will elucidate whether decreases in BMD among HIV-infected mothers on lifetime ART are exacerbated with repeat pregnancy/breastfeeding and if BMD recovery after breastfeeding is further decreased when compared to HIV-negative women at the end of breastfeeding. The long-term goal of this cohort study is to better support the bone health of breastfeeding women living with HIV who are on lifetime ART. The requested administrative supplement will allow completion of the crucial 36 month outcomes.