Depot medroxyprogesterone acetate (DMPA) and TDF-based PrEP have been associated with reductions in bone mineral density (BMD) when used consistently over multiple years. The effect of concurrent PrEP and DMPA on declines in BMD in young women who have not yet reached peak bone mass is unknown. A 2-year prospective observational study was conducted with women aged 16-25 years in Uganda who were provided either condoms or injectable DMPA for contraception and either condoms or FTC/TDF as oral PrEP for HIV prevention. Overall, 499 women were included with median age of 20 years (IQR 18-21) and normal baseline distribution of BMD z-scores. Women using neither agents (n=39) experienced BMD growth of 2.01% at lumbar spine, 1.22% at hip, 0.10% at femoral neck. Women with consistent use of both agents during 1 year (n=22) experienced an average BMD loss of 1.04% in the lumbar spine and hip and 1.77% in femoral neck. These losses were statistically different relative to women who used neither agent: difference in % BMD change of -3.05% at the lumbar spine (95% CI -4.77%, -1.33%, p=0.001), -2.26% in total hip (95% CI -3.38%, -0.69%, p=0.006) and approached significance at the femoral neck (-1.87%, -3.84%, 0.11%, p=0.067). This study observed a trend for women with concurrent DMPA and PrEP use to have 1-3% lower BMD than unexposed women after 12 months. Further work is needed to quantify the impact of longer concurrent exposure to TDF-based PrEP and DMPA.

Depot medroxyprogesterone contraceptive use has been shown to result in a doubling of bone mineral density (BMD) loss in women living with HIV initiating TDF-containing antiretroviral treatment. This study determined whether BMD does recover when these women are switched to TAF-containing antiretroviral treatment over a two-year period. Women living with HIV on depot-medroxyprogesterone contraception were randomized to either continue on a TDF based antiretroviral treatment (n= 108) or to switch to B/F/TAF (n = 111) for 2 years. A third group of women on TDF and using non-hormonal contraception were offered B/F/TAF (n= 125). Both on-hormonal and depot medroxyprogesterone groups who switched to B/F/TAF had significant improvement in mean % BMD post switch with no significant differences. However, depot medroxyprogesterone users had lower mean BMD Z-scores at baseline and these remained lower compared to non-hormonal users at the lumbar spine -0.805 vs -0.131; total hip -0.835 vs -0.432 and femoral neck -0.794 vs -0.428, P <0.021. In women living with HIV receiving TDF-containing antiretroviral treatment, switching to B/F/TAF was associated with significant improvement in mean % BMD underscoring the promising role of newer bone-sparing antiretroviral drugs in minimizing comorbid risks. However, compared to non-hormonal users, depot medroxyprogesterone users had lower BMD Z-scores at all-time points. Additional research should focus on the impact of interventions that preserve BMD for depot medroxyprogesterone users on antiretroviral treatment, including alternative contraceptive methods.

Tenofovir-DF (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). This prospective cohort study aimed to assess the combined effects of DMPA-IM and TDF on BMD in young adult women living with HIV over two years compared with age-matched people without HIV. The study enrolled women aged 18-35 years from 11 HIV care and general health facilities in Kampala. The participants were classified into four groups as follows: women living with HIV initiating TDF-containing antiretroviral therapy with DMPA-IM (n=159); women living with HIV using DMPA-IM but not eligible for ART (n=187); women living with HIV initiating TDF-containing ART without DMPA-IM (n=106); and controls without HIV using non-hormonal contraceptives (n=69). BMD of the lumbar spine, total hip, and femoral neck were measured at enrolment and at intervals every 6 months thereafter. BMD was shown to decline significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (-3.4% vs -1.11%), total hip (-3.9% vs 1.7%) and femoral neck (-4-4% vs -2.0%. BMD increased in controls at the lumbar spine (1.5% change), and remained unchanged at total hip and femoral neck. The concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline than TDF alone (lumbar spine -2.7%; total hip -2.5% and femoral neck -2.9%) or than controls (lumbar spine -4.9%; total hip -4.2%; and femoral neck -4.8%. The concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART.