The purpose of this study was to learn if women taking the ritonavir and other HIV medications in the class of protease inhibitors have lower levels of a birth control medication called norethindrone. Norethindrone (also called the mini pill) is an FDA (Food and Drug Administration) approved progestin-only birth control pill used to prevent pregnancy. Norethindrone is the standard medication used in women who take the progestin only pill to prevent pregnancy. There are other birth control pills which contain different medications. The investigators learned that certain HIV medications (ritonavir and other protease inhibitors) make the blood level of this birth control pill higher. Based on these findings the progestin only pill with norethindrone will likely prevent pregnancy in HIV positive women taking protease inhibitors.
Objective: Pharmacokinetic interactions exist between combined oral contraceptives and protease inhibitors (PI). However, such information is lacking for progestin-only oral contraception. We sought to define the steady-state pharmacokinetic interaction between norethindrone (NET) and PI in HIV-infected women.
Methods and Design: We conducted an open-label, prospective, nonrandomized trial to characterize the steady-state pharmacokinetics of serum NET in HIV-infected women receiving PI compared with a control group of HIV-infected women receiving other noninteracting drugs. After 21 days of 0.35 mg of NET ingestion once daily, serial serum samples were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours. The area under the curve between 0 and 72 hours after ingestion was calculated by trapezoidal approximation.
Results: Thirty-five women were enrolled, 2 withdrew. Sixteen women in the PI group and 17 controls completed the study. NET half-life and maximum concentration were not significantly different between the 2 groups. Minimum concentration of NET was significantly higher in the PI group (P = 0.01). The ratio of the geometric mean NET area under the curve in the PI group compared with controls was 1.5 (90% confidence interval: 1.21 to 1.86). NET serum concentrations were significantly higher in HIV-infected women taking a PI compared with controls (P = 0.004).
Conclusions: Coadministration of PI inhibits NET metabolism as shown by higher serum NET area under the curve levels, a surrogate marker for therapeutic contraceptive efficacy. This study supports the increased utilization of progestin-only pills in HIV-infected women receiving certain PI regimens.