Contraception is a critical component of healthcare for HIV-infected women as it is key to both promoting maternal health and preventing perinatal transmission, yet evidence to direct contraceptive choices in HIV-positive women remains limited. Particular concern exists about potential effects of protease inhibitors, especially ritonavir, on the efficacy of combined oral contraceptives. However, these concerns arise from pharmacokinetic data obtained from small studies; no existing studies systematically evaluate ovulation in oral contraceptive users on ritonavir. Thus, a study correlating the effects of ritonavir on combined oral contraceptive pharmacokinetics with data on ovulation could provide important information to guide contraceptive use in women taking protease inhibitors.
The proposed project is a two-arm prospective cohort and pharmacokinetic study comparing levonorgestrel and ethinyl estradiol pharmacokinetics in HIV-positive women taking antiretroviral regimens that include ritonavir to those in women who take regimens known not to interact with combined oral contraceptives. In addition, the prevalence of ovulation will be measured in each group. Participants will take a combined oral contraceptive containing levonorgestrel and ethinyl estradiol for 21 days, during which they will undergo twice-weekly serum progesterones. On the final day, they will complete a pharmacokinetic study. We hypothesize that levonorgestrel levels, as measured by area-under-the-curve from 0 to 72 hours, will be increased in women on ritonavir, while ethinyl estradiol levels will be decreased and ovulation, defined by a serum progesterone of at least 3 ng/mL, will be unchanged.
This study will be the first to evaluate the effects of ritonavir on the pharmacokinetics of a combined oral contraceptive containing the progestin levonorgestrel. In addition, no previous studies have rigorously assessed ovulation in women taking protease inhibitors and combined oral contraceptives. As a result, this study will provide new information correlating pharmacokinetic changes with effects on ovulation.
The primary challenge we anticipate encountering is participant recruitment and retention, as the study requires a number of site visits, each entailing a blood draw. Similarly, participants will need to complete a 12-hour pharmacokinetic visit, which may be logistically challenging. Finally, women must be ovulatory, as determined by serum progesterone, prior to study entry, which will likely require screening a greater number of potential participants to reach target study size.