A parallel group pharmacokinetic study was conducted to examine drug interactions with doravirine-containing regimens among women of reproductive potential living with HIV. Participants on doravirine/lamivudine/tenofovir-DF self-selected concomitant contraception: intramuscular depo-medroxyprogesterone acetate (IM DMPA) (group 1, n=21), etonogestrel implant (group 2, n=21) or copper intrauterine device (group 3). The comparator groups were on dolutegravir + IM DMPA (group 4, n=21) and a historical dolutegravir + etonogestrel implant (group 5, n=24). GM Cmin MPA concentrations for groups 1 and 4 were 561 and 551 pg/mL, respectively (GMR 1.01, 90% CI 0.82, 1.24; adjusted GMR 1.05, 90% CI 0.83, 1.34). GM Ctrough etonogestrel concentrations for groups 2 and 5 were 312 and 225 pg/mL, respectively (GMR 1.15, 90% CI 1.04, 1.28; adjusted GMR 1.16, 90% CI 1.04, 1.30). Doravirine did not have significant effects on MPA and etonogestrel contraceptives. This study did not detect significant effects of doravirine-containing ART on DMPA or etonogestrel contraceptives. 

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.