Bone Mineral Density, Body Composition, and Mineral Homeostasis Over 24 Months in Urban South African Women With HIV Exposed to Antiretroviral Therapy

Abstract

Human immunodeficiency virus-(HIV-) infection and antiretroviral therapy (ART) exposure are associated with bone loss. African data are limited despite the region's HIV burden. Of 247 ART-naïve, premenopausal, urban, black African women aged 33.9 AE 6.6 years from Soweto, South Africa, measured at baseline, 110 underwent anthropometry, DXA, and blood and urine collections at 12 and 24 months; 39 were HIV-negative (Nref), 28 were people with HIV (PWH) not ART-exposed for the duration of the study (ART-N), and 43 were PWH who were ART-exposed within the first 12 months (ART-Y). At baseline, the ART-Y group had lower BMI and fat mass than the Nref group. Within 12 months of ART initiation, areal bone mineral density (aBMD) had decreased at the lumbar spine and at the whole body less head, despite increased weight, and hip aBMD had not increased in line with the Nref group. There was no evidence of further bone changes between 12 and 24 months. By 24 months, the ART-Y women had gained weight and fat mass, but remained lighter with less fat than the Nref women. ART initiation normalized the low serum albumin of the ART-Y group at baseline, but was associated with elevated bone turnover markers at 12 and 24 months. Vitamin D status and renal phosphate handling were normal. ART-N had similar aBMD and other characteristics to the Nref group throughout, except unlike the Nref group, weight and fat mass did not increase and serum albumin decreased. This study in African women of childbearing age demonstrated that the bone loss that had occurred in these PWH after ART initiation did not continue after 12 months and that bone loss did not occur in ARTunexposed PWH over 2 years. At 24 months, despite gains in weight and fat mass, ART-exposed women remained lighter, with lower aBMD, fat mass, and higher bone turnover than women without HIV. More studies are required to establish if the bone loss and fat gain reverse, stabilize, or continue with further ART exposure, particularly during and after menopause.

Changes in Bone Mineral Density During and After Lactation in Ugandan Women With HIV on Tenofovir-Based Antiretroviral Therapy

“…The sample size for the current study was calculated for the LS aBMD because most evidence from lactation studies ( 14,15,23 ) shows greater changes in aBMD at the LS—a trabecular‐rich site—compared to other skeletal sites. We, therefore, hypothesized that if there is an additive effect of lactation and ART on bone mineral mobilization, the changes in aBMD would be more accentuated at the LS.…”

“…( 7 ) Globally, 1.1 million pregnant WWH (80%) received antiretroviral agents for PMTCT in 2018, and over 90% were living in Africa. ( 8 ) Few longitudinal HIV/ART and bone studies using dual‐energy X‐ray absorptiometry (DXA) have been conducted in African women ( 9–14 ) ; hence, data are limited in pregnant and breastfeeding women on triple ART.…”

Hard facts and misfits: essential ingredients of public health nutrition research

“…In Eastern and Southern Africa, where tenofovir disoproxil fumarate-based ART is commonly prescribed, women have the highest burden of HIV infection and, because of ART, women living with HIV are now likely to live into and beyond the menopause. Our recent study in Soweto, South Africa, among women with good vitamin D status, showed the expected bone mineral loss in those living with HIV after the initiation of ART (48) . However, we found no evidence of an effect on their vitamin D status.…”

Bone Loss and Lactation in Women Living With HIV: Potential Implications for Long-Term Bone Health

“…The success of anti‐retroviral treatments (ART) is of particular concern given that treatment is often initiated during childhood, adolescence, or early adulthood, likely impacting bone health during development or midlife. ( 1–4 ) In the current issue of JBMR , Nabwire and colleagues present findings of a study of the impact of the diagnosis and initiation of treatment during pregnancy on lactation‐associated bone loss in Ugandan women living with and without HIV. ( 5 ) Before discussing these data, it is pertinent to describe the evidence for bone loss on initiation of ART in premenopausal women who are neither pregnant nor lactating.…”

“…On initiation of treatment, women treated with ART lost 2% to 3% bone mineral density (BMD) over 12 months, around double the changes found in early menopause. ( 3 ) A further 12 months later, these differences remained at the lumbar spine and whole body, indicating lasting deficits in BMD, ( 4 ) but no further loss had occurred, suggesting the bone had reached a steady state after the initial impact of initiation of ART. If these effects remain, it is clear that by the time these women reach menopause, they will be at further risk of bone loss and increased risk of fragility fracture.…”