Efavirenz, in Contrast to Nevirapine, is Associated With Unfavorable Progesterone and Antiretroviral Levels When Coadministered With Combined Oral Contraceptives

Abstract

Effective contraception has been widely promoted for HIV-positive women. However, there are limited data on the interactions between combined hormonal contraceptives and nonnucleoside reverse transcriptase inhibitors . This study assessed the steady-state contraceptive effectiveness and safety of combined oral contraceptive (COC) containing 0.150 mg desogestrel /0.030 mg ethinyl estradiol with either nevirapine (NVP) or efavirenz (EFV) in 34 HIV-positive women. The targeted level for contraceptive effectiveness was endogenous progesterone level < 3.0 ng/mL. We measured NVP/EFV plasma concentrations 12 hours after administration (C12) with and without COC. The desired therapeutic levels were >3.1 mg/L for NVP and 1.0-4.0 mg/L for EFV, respectively. All 18 subjects in the NVP group had serum progesterone <1.0 ng/mL. Four of 16 subjects (25%) in the EFV group had serum progesterone >1.0 ng/mL, including 3 subjects with >3.0 ng/mL (might indicate ovulation). The difference in progesterone levels between the 2 groups was statistically significant (P = 0.04). The median C12 of NVP increased insignificantly by 17% with COC; the median C12 of EFV decreased significantly (P = 0.02) by 22%. In 3 of 16 subjects (19%) in the EFV group, C12 of EFV dropped below 1.0 mg/L. In contrast to NVP, coadministrating desogestrel/ethinyl estradiol containing COC with EFV was associated with unfavorable progesterone and antiretroviral levels. Our results suggest that NVP may be superior to EFV when used with COC in HIV-positive women.