Nadia Kancheva Landolt1, Torsak Bunupuradah, Pope Kosalaraksa, Sasiwimol Ubolyam, Narukjaporn Thammajaruk, Serge Cremers, Roseann Zott, Stephen Kerr, Jintanat Ananworanich. 1. *Medical Department, The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand; †Medical Pediatric Department, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ‡Research Biomarkers Core Laboratory, Irving Institute for Clinical and Translation, Columbia University Medical Center, New York, NY; §Biostatics, Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands; ‖The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ¶SEARCH, Bangkok, Thailand; and #Currently, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
Abstract
BACKGROUND: We report the pharmacokinetic interactions of combined oral contraceptive (COC) containing ethinyl estradiol (EE2)/desogestrel (DSG) with lopinavir/ritonavir (LPV/r) in 16 HIV-positive adolescents. METHODS: We measured Ctrough of EE2 and etonogestrel (ENG), the active metabolite of DSG, in HIV-positives on LPV/r-based ART; Ctrough of LPV/r with and without COC; endogenous progesterone. EE2/ENG levels were compared with our own historical data of HIV-negative controls. RESULTS: Ctrough of EE2 and ENG varied from 3 to 57 pg/mL and from 1051 to 5000 pg/mL, respectively. The geometric mean ratios (GMR) of Ctrough in HIV-positives on LPV/r with COC versus HIV-negative controls with COC only were 0.68 (95% CI: 0.42 to 1.08) or 32% decreased (P = 0.10) for EE2; and 1.08 (95% CI: 0.73 to 1.60) or 8% increased (P = 0.68) for ENG. Endogenous progesterone was <1.0 ng/mL in all participants, consistent with anovulation. Ctrough of LPV decreased statistically insignificantly with COC and remained above the desired therapeutic minimum of 1.0 mg/L in all. CONCLUSIONS: The study found no clinically relevant interaction between EE2/DSG and LPV/r. This was supported by suppressed ovulation, assessed by low endogenous progesterone levels in all participants; and preserved antiretroviral activity, assessed by LPV/r levels above the desired therapeutic minimum in all participants. However, the high variability of hormonal levels warrants individual monitoring and further investigation. Condom use should always be encouraged for infection prevention.
BACKGROUND: We report the pharmacokinetic interactions of combined oral contraceptive (COC) containing ethinyl estradiol (EE2)/desogestrel (DSG) with lopinavir/ritonavir (LPV/r) in 16 HIV-positive adolescents. METHODS: We measured Ctrough of EE2 and etonogestrel (ENG), the active metabolite of DSG, in HIV-positives on LPV/r-based ART; Ctrough of LPV/r with and without COC; endogenous progesterone. EE2/ENG levels were compared with our own historical data of HIV-negative controls. RESULTS: Ctrough of EE2 and ENG varied from 3 to 57 pg/mL and from 1051 to 5000 pg/mL, respectively. The geometric mean ratios (GMR) of Ctrough in HIV-positives on LPV/r with COC versus HIV-negative controls with COC only were 0.68 (95% CI: 0.42 to 1.08) or 32% decreased (P = 0.10) for EE2; and 1.08 (95% CI: 0.73 to 1.60) or 8% increased (P = 0.68) for ENG. Endogenous progesterone was <1.0 ng/mL in all participants, consistent with anovulation. Ctrough of LPV decreased statistically insignificantly with COC and remained above the desired therapeutic minimum of 1.0 mg/L in all. CONCLUSIONS: The study found no clinically relevant interaction between EE2/DSG and LPV/r. This was supported by suppressed ovulation, assessed by low endogenous progesterone levels in all participants; and preserved antiretroviral activity, assessed by LPV/r levels above the desired therapeutic minimum in all participants. However, the high variability of hormonal levels warrants individual monitoring and further investigation. Condom use should always be encouraged for infection prevention.
Authors: Kimberly K Scarsi; Kristin M Darin; Catherine A Chappell; Stephanie M Nitz; Mohammed Lamorde Journal: Drug Saf Date: 2016-11 Impact factor: 5.606