Clinical research in women's reproductive health and the human immunodeficiency virus

Abstract

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: I conducted an open-label, prospective, non-randomized trial to characterize the steady-state pharmacokinetics of serum NET in HIV infected women receiving PI compared to a control group of HIV infected women receiving other types of antiretroviral therapy that does not alter NET levels. Following 21 days of NET 0.35 mg ingestion once daily, serial serum samples were obtained at 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, two 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 two 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 to controls was 1.5 (90% confidence interval 1.21-1.86). NET serum concentrations are significantly higher in HIV infected women taking a PI compared to controls (p=0.004).

Conclusions: Co-administration 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 increased utilization of progestin only pills in HIV infected women receiving PI.