To evaluate pharmacokinetics and pharmacogenetics of contraceptive implant progestin concentrations in HIV-positive women initiating efavirenz- or nevirapine-containing antiretroviral therapy (ART).
We analyzed stored samples from women self-reporting implant use in the Partners PrEP Study.
Plasma samples collected every six months were analyzed for levonorgestrel and etonogestrel concentrations. Progestin concentrations from samples collected after ART initiation were compared to pre-ART concentrations for intraindividual comparisons. We used adjusted linear mixed models to compare hormone concentrations between individuals on efavirenz and nevirapine to a no ART group. We then evaluated whether possessing certain alleles with known or possible influences on efavirenz, nevirapine, or progestin metabolism were associated with changes in progestin concentrations or modified the association between ART use and progestin concentrations.
Our analysis included 11 women who initiated efavirenz, 13 who initiated nevirapine, and 36 who remained ART-naïve. In the efavirenz group, the adjusted geometric mean ratio (aGMR) of levonorgestrel was 0.39 (90% confidence intervals (0.31, 0.49); p < 0.001) and the etonogestrel aGMR was 0.51 (0.34, 0.76); p = 0.006) compared to the control group. No difference was observed in the nevirapine group compared to controls (levonorgestrel 0.93 (0.74, 1.18); p = 0.64; etonogestrel 1.07 (0.77, 1.50); p = 0.73). Possession of four allele variants were found to result in further reductions in progestin concentrations among those receiving efavirenz.
Concomitant use of efavirenz significantly reduces levonorgestrel or etonogestrel concentrations by 61% and 49%, respectively, compared to no ART use. We also report allelic variants in hepatic enzymes that influenced the extent of the observed drug-interaction between progestins and efavirenz.
aDepartment of Medicine
bDepartment of Global Health
cDepartment of Epidemiology
dDepartment of Obstetrics and Gynecology, School of Pharmacy, University of California, San Francisco, San Francisco, California, USA
eEndocrine Technologies Core, Oregon National Primate Research Center, Beaverton, Oregon, USA
fDepartment of Pharmaceutics, University of Washington, Seattle, Washington, USA
gGlobal Health, Population, and Nutrition, FHI 360, Durham, North Carolina, USA
hDivision of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
iCenter for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya
jDepartment of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, Nebraska, USA.
*Members of the study team listed after the Acknowledgements
Correspondence to Rena C. Patel, UW Box 359927, 325 Ninth Avenue, Seattle, WA, 98104. Tel: +206 520 3800; e-mail: firstname.lastname@example.org
Received 27 March, 2019
Revised 28 May, 2019
Accepted 31 May, 2019