Medroxyprogesterone acetate levels among Kenyan women using depot medroxyprogesterone acetate in the FEM-PrEP trial

Kavita Nanda,Rebecca Callahan,Douglas Taylor,Meng Wang,Kawango Agot,David Jenkins,Lut Van Damme,Laneta Dorflinger

doi:10.1016/j.contraception.2016.03.003

Abstract

ObjectiveTo describe medroxyprogesterone acetate (MPA) levels among Kenyan depot medroxyprogesterone acetate (DMPA) users in the FEM-PrEP HIV prevention trial, and to compare MPA levels between ARV for HIV prevention (treatment) and placebo groups. Study DesignWe measured MPA in previously collected plasma samples from 63 Kenyan trial participants who used DMPA for one or two complete intervals. We separately assessed MPA levels among the nine DMPA users who became pregnant at this site. ResultsMean MPA levels at the end of each 12week injection interval were 0.37ng/ml (95% CI: 0.25, 1.99) and 0.28ng/ml (95% CI: 0.19, 1.22) among participants assigned TDF/FTC and 0.49 (95% CI: 0.40, 1.27) and 0.39 (95% CI: 0.31, 1.17) among those assigned placebo. The difference between groups was not statistically significant overall, or in an analysis which adjusted for the observed low adherence to TDF/FTC. Unanticipated findings of this analysis were low 12-week MPA levels among DMPA users in both study arms. Of 61 women who contributed data for the first DMPA injection interval, 26.2% had MPA levels<0.1ng/ml and 9.8% had levels below the detection level (0.02ng/ml) at 12weeks post-injection. Levels were similar at the end of the second injection interval. Five of nine women who became pregnant had levels below 0.15ng/mL at the time of their last negative pregnancy test. ConclusionsUse of TDF/FTC did not appear to affect serum MPA levels, however we found lower than expected MPA concentrations at the end of the dosing interval among DMPA users in the FEM-PrEP trial, the cause of which are unknown. ImplicationsThis study presents some of the few available data on MPA levels among DMPA users in Africa. The low levels among users described here, together with a number of pregnancies among DMPA users, are potentially concerning and require further investigation.

Highlights

Around the world an estimated 48 million women rely on injectable contraceptives for pregnancy prevention [1,2]
For each participant contributing a complete set of data, we used a linear trapezoidal procedure to compute a crude area under the curve (AUC) from the injection visit through the end of the 12-week dosing interval
We excluded interval 1 or interval 2 data from two women indicating either no injection had occurred or results strongly indicating that the injection was given before drawing of the 12-week blood sample, leaving 61 women contributing data to the first interval of depot-medroxyprogesterone acetate (DMPA) use, 49 women contributing to a second interval of use, 62 women contributing to at least one interval, and a total of 110 intervals of use (65 Placebo, 45 TDF/FTC; Fig. 1)

Summary

Introduction

Around the world an estimated 48 million women rely on injectable contraceptives for pregnancy prevention [1,2]. We noted several unexpected pregnancies among DMPA users in the Bondo, Kenya site of the FEM-PrEP Trial for HIV Prevention among African Women. These pregnancies, along with higher overall pregnancy rates among women randomized to tenofovir/emtricitabine (TDF/FTC) [5], raised concerns that use of the study drug could be interfering with the effectiveness of hormonal contraceptives. Even though TDF/FTC is not known to be a hepatic enzyme inducer, and would not be expected to affect contraceptive efficacy, we were concerned about potential interactions other than hepatic enzyme induction In response to this concern, we evaluated MPA levels in a sub-sample of DMPA users, and compared MPA levels by study arm. We evaluated MPA levels in women who conceived while using DMPA

Methods

Results

Conclusion