119 – Dolutegravir Does Not Reduce Levonorgestrel or Medroxyprogesterone Acetate Concentrations in WLWH

Background

Drug-drug interactions (DDIs) between contraceptives and antiretroviral therapy (ART) may increase the risk of unintended pregnancy and side effects. The levonorgestrel (LNG) implant and depot medroxyprogesterone acetate (DMPA) injectable are commonly used contraceptives in women living with HIV (WLWH), but pharmacokinetic (PK) data evaluating DDIs between dolutegravir (DTG) and LNG or MPA are lacking.

Methods

We conducted a phase 4 non-randomised, parallel-arm, open-label PK study among non-pregnant WLWH on DTG-based ART and HIV-negative, ART-naïve women in Botswana, who chose to initiate the LNG implant or DMPA injectable (n=140; 70 LNG, 70 DMPA; 35 WLWH per arm). Blood was sampled before contraceptive initiation and at 2-4 weekly intervals. A pregnancy test and data on safety and tolerability were collected each visit. Area under the concentration-time curves of LNG over 24 weeks (LNG AUC_24weeks) and MPA over 12 weeks (MPA AUC_12weeks) were compared between WLWH on DTG-based ART and HIV-negative, ART-naïve women using geometric mean ratios (GMR).

Results

Median (range) LNG AUC_24weeks was 13732 (6252-46797) pg.week/mL and 10157 (3922-36311) pg.week/mL in WLWH on DTG-based ART and HIV-negative women respectively; GMR 1.30, 95% CI 0.99-1.68. Median (range) MPA AUC_12weeks was 10770 (4665-20005) pg.week/mL and 10212 (3018-18122) pg.week/mL in WLWH on DTG-based ART and HIV-negative women respectively; GMR 1.09, 95% CI 0.91-1.32. LNG C_max was higher in WLWH on DTG compared to HIV-negative women (GMR 1.71, 95% CI 1.01-2.89), while MPA C_max was similar between groups (GMR 1.16, 95% CI 0.92-1.47). There was no difference in median DTG concentrations before and after LNG (2155 vs. 2774pg/ml, p=0.09) or MPA (3358 vs. 3244pg/ml, p=0.46). Both contraceptive methods were well-tolerated, with no unintended pregnancies or serious adverse events. Endogenous progesterone was suppressed (<0.7 nmol/L) in 93% of WLWH on DTG vs. 78% HIV-negative women using LNG implant at 24 weeks, p=0.09; and 94% of WLWH on DTG vs. 87% HIV-negative women using DMPA injectable at 12 weeks, p=0.35.

Conclusions

There are no clinically significant DDIs between DTG-based ART and the LNG implant or DMPA injectable. DTG does not reduce LNG or MPA concentrations; and the LNG implant and DMPA injectable do not reduce DTG levels in WLWH. The LNG implant and DMPA injectable are both highly effective, safe and well-tolerated contraceptive options for WLWH on DTG-based ART.

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