Impact of estrogen replacement therapy on bone health in an aging population of women living with HIV

PROJECT SUMMARY / ABSTRACT Current antiretroviral therapy (ART) regimens have rendered HIV a manageable chronic condition rather than a fatal disease, with people who initiate ART soon after infection achieving nearly normal life expectancy. As a consequence of increased survival, more women living with HIV (WLWH) will now undergo menopause and be subject to a disease burden that reflects age along with adverse skeletal consequences of postmenopausal estrogen deficiency. In addition to known bone loss and increased fracture risk in postmenopausal women, ART also causes negative impacts on bone. Therefore ART-suppressed WLWH may have a compounded detrimental effect on bone due to long-term ART treatment combined with menopause. We hypothesize that treatment with estrogen replacement will attenuate the increased rate of bone loss during menopause and improve bone health even with congruent administration of ART. We will address this hypothesis using a previously NIH-funded project that employs a novel non-human primate model that replicates the sequence of acute infection, ART initiation, chronic suppressed infection, and subsequent menopause now characteristic of a growing proportion of aging WLWH. We intend to measure the impact of ART-suppression and menopause, with and without hormone replacement therapy, on bone architecture and quality. Furthermore, we will determine whether bone marrow, a known HIV reservoir, is deficient in necessary bone cell precursors. In conclusion, these studies will examine bone health in an aging population of WLWH and potentially inform future care options utilizing hormone replacement therapy to protect these women from compounded risk of bone fractures and osteoporosis.