Depo-Provera worsens bone loss with TDF-containing ART initiation in young women
BACKGROUND: Antiretroviral therapy (ART) initiation with tenofovir disoproxil fumarate (TDF) is associated with bone mineral density (BMD) loss. Among women of reproductive age, depot medroxyprogesterone acetate (DMPA, Depo Provera) also negatively impacts BMD. Our goal was to determine the combined BMD effects of DMPA and TDF initiation in young women over two years, compared to a matched HIV-uninfected group.
METHODS: Women were recruited from 11 HIV care centers and general health facilities around Kampala, Uganda and classified based on their combination of HIV status, TDF use and DMPA use. We compared 3 groups: women initiating TDF-containing ART with (HIV+/DMPA+/TDF+) and without DMPA (HIV+/DMPA-/TDF+) and an HIV-uninfected control group not taking DMPA (HIV-/-DMPA-/TDF)-. All HIV+ women were ART-naïve at baseline. BMD assessments of lumbar spine(LS), total hip(TH) and femoral neck(FN) were done using dual energy x-ray absorptiometry at 6-monthly intervals. We used repeated measures analyses to compare rate of change, calculated as percent (%) change in BMD/ year.
RESULTS: Between March 2015 and October 2017, we enrolled 265 HIV-infected women initiating TDF-containing ART (159 DMPA users, 106 non-hormonal users), and 69 uninfected. Median age was 26 years. Baseline BMD was not significantly different from that of HIV-uninfected controls. Annualized rates of BMD loss were higher in HIV-infected women with greatest loss occurring in DMPA users compared to HIV-infected non-hormonal users, or uninfected controls at all sites: 4.0%(-4.4, -3.6 ) vs. -1.8%(-2.2, -1.4) vs. 0.8%(0.4, 1.1) at LS, -2.1%(-2.3, -1.9) vs. -0.9%(-1.1, -0.6) vs. â??0.0%(-0.4, 0.3) TH, and -2.5%(-2.8, -2.2) vs. -1.0%(-1.3,-0.7) vs. 0.1%(-0.3, 0.5) FN respectively. These changes were significantly different between the three groups, all p-values <0.05(figure).
CONCLUSIONS: Concomitant DMPA use was associated with a doubling of BMD loss in young women initiating TDF-containing ART. Newer treatment bone sparing regimens like tenofovir alafenamide-based ART may mitigate BMD loss and early aging among HIV-infected women.
F.K. Matovu * (1,2,3), J.A. Babirye (1), M. Nabwana (1), P. Musoke (4,1), M. Beksinska (5), J.M. Pettifor (6), M.G. Fowler (7), T.T. Brown (8), for the BONE:CARE Study Team
(1) Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda, (2) Makerere University College of Health Scienced, School of Public Health, Kampala, Uganda, (3) Consortium for Advanced Research and Training in Africa/ University of Witwatersrand, Johannesburg, South Africa, (4) Makerere University College of Health Sciences, Department of Pediatrics and Child Health, Kampala, Uganda, (5) Maternal Adolescent & Child Health (MatCH) Research, Johannesburg, South Africa, (6) University of the Witwatersrand, Department of Paediatrics, Johannesburg, South Africa, (7) Johns Hopkins University School of Medicine, Department of Pathology, Baltimore, United States, (8) Johns Hopkins University, Division of Endocrinology, Diabetes, and Metabolism, Baltimore, United States