Bone Mineral Density in Antiretroviral Therapy‐Naïve HIV‐1–Infected Young Adult ‐Women Using Depot Medroxyprogesterone Acetate or Nonhormonal Contraceptives in Uganda

Abstract

Most studies evaluating BMD in human immunodeficiency virus (HIV)‐infected populations have focused on antiretroviral therapy (ART)‐experienced patients. In this study, the association between HIV‐1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV‐1–infected women in a resource‐limited setting was assessed before long‐term exposure to ART. The data were then compared with that of the 2005–2008 United States National Health and Nutrition Examination Survey data for non‐Hispanic White and Black women. Women aged 18–35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV‐1 status and DMPA use: (i) HIV‐1–infected current DMPA users, (ii) HIV‐1–infected previous DMPA users, (iii) HIV‐1–infected nonhormonal‐contraceptive users, and (iv) HIV‐uninfected nonhormonal‐contraceptive users. All HIV‐1–infected women reported being ART‐naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV‐1 and/or DMPA and BMD Z‐scores. Baseline data were analyzed for 452 HIV‐1–infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV‐1–uninfected nonhormonal‐contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12‐48]. A higher proportion of HIV‐1–infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z‐score ≤−2 at any of the three sites) compared with age‐matched HIV‐1–uninfected women (2.9%). HIV‐1 infection and DMPA use were independently associated with significantly lower mean BMD Z‐scores at all sites, with the greatest difference being among HIV‐1–infected current DMPA users (5.6%–8.0%) versus uninfected nonhormonal users. Compared with non‐Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV‐1–infected women in resource‐limited settings. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Calcium deficiency worldwide: prevalence of inadequate intakes and associated health outcomes

“…77 A recent study from Kampala, Uganda, in East Africa, comparing the BMD of premenopausal Black women with the NHANES reference database, found that mean lumbar spine BMD was 1.2 SD below the mean for U.S. Black women and 0.8 SD below that of U.S. white women, while at the femoral neck, the BMD was 0.4 SD below that of U.S. Black women but 0.1 SD above that of U.S. white women. 78 In West Africa, a study of pre and postmenopausal Gambian women revealed that after correcting for age, weight, and height, bone mineral content at the lumbar spine was on average 24% lower than that of white women in the UK. The reduction in bone mineral content increased to 42% in those >64 years of age.…”

Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda

“… 15 Indeed in our baseline analysis, we observed lower BMD among ART-naive current DMPA-IM users compared with previous users and non-users. 18 Similar to the mechanism of TDF-associated BMD loss, studies of bone turnover in DMPA-IM users have suggested that the effects of DMPA-IM on the skeleton are at least partially mediated through increased bone resorption and reduced formation. 23 , 24 Although we only obtained incomplete data (6 months rather than 2 years) on BMD loss among women living with HIV using DMPA-IM before ART initiation, we demonstrate significant declines in BMD in this group compared with the control group without HIV at the lumbar spine at 24 weeks.…”

“…Regardless of their HIV infection status, women were excluded if they had been pregnant or breastfeeding in the past 6 months before enrolment, had intented to become pregnant during the 2-year study, or had a pre-existing medical condition known to affect bone metabolism. 18 …”

“… 20 Details on the DXA software, Z score estimation, and quality-control measures have been previously described. 18 …”

“…Regardless of their HIV infection status, women were excluded if they had been pregnant or breastfeeding in the past 6 months before enrolment, had intented to become pregnant during the 2-year study, or had a pre-existing medical condition known to affect bone metabolism. 18 ART was provided by primary health-care facilities in accordance with the Uganda National ART guidelines at the time that recommended initiation of TDF, lamivudine and efavirenz, or nevirapine for people living with HIV with a CD4 count of up to 500 cells/µL or WHO stage 3 or higher. 17 In February, 2017, new guidelines were implemented in Uganda that eliminated all restrictions on ART initiation among people living with HIV.…”