Interactions between etonogestrel-releasing contraceptive implant and 3 antiretroviral regimens

Autor: Regis Kreitchmann, Jiajia Wang, Nahida Chakhtoura, Alice Stek, Edmund V. Capparelli, Ahizechukwu C. Eke, David Shapiro, Mark Mirochnick, Brookie M. Best, Impaact P s Protocol Team
Rok vydání: 2022
Předmět:
IMPAACT P1026s protocol team
Human immunodeficiency virus (HIV)
HIV Infections
medicine.disease_cause
Lopinavir
chemistry.chemical_compound
immune system diseases
heterocyclic compounds
Obstetrics
Long-acting reversible contraceptives
virus diseases
Obstetrics and Gynecology
Drug Combinations
Infectious Diseases
6.1 Pharmaceuticals
Public Health and Health Services
HIV/AIDS
Female
Infection
Contraceptive implant
medicine.drug
medicine.medical_specialty
Efavirenz
Anti-HIV Agents
Atazanavir Sulfate
Clinical Sciences
Atazanavir
Paediatrics and Reproductive Medicine
Cmin
Contraceptive Agents
Pharmacokinetics
parasitic diseases
medicine
Humans
Obstetrics & Reproductive Medicine
Etonogestrel
Ritonavir
Desogestrel
business.industry
Prevention
Evaluation of treatments and therapeutic interventions
HIV Protease Inhibitors
biochemical phenomena
metabolism
and nutrition
Good Health and Well Being
Reproductive Medicine
chemistry
business
Zdroj: Contraception. 105:67-74
ISSN: 0010-7824
DOI: 10.1016/j.contraception.2021.08.006
Popis: ObjectivesLong-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, and efavirenz pharmacokinetics.Study designWe enrolled postpartum women using etonogestrel implants and receiving ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, or efavirenz-based regimens between 2012 and 2015. Etonogestrel implants were inserted 2 to 12 weeks postpartum. We performed pharmacokinetic sampling pre-etonogestrel insertion and 6 to 7 weeks postinsertion. We measured antiretroviral concentrations pre and postetonogestrel insertion, and compared etonogestrelconcentrations between antiretroviral regimens. We considered a minimum serum etonogestrelconcentration of90 pg/mLadequate for ovulation suppression.ResultsWe collected pharmacokinetic data for 74 postpartum women, 22 on ritonavir-boosted-atazanavir, 26 on ritonavir-boosted-lopinavir, and 26 on efavirenz. The median serum concentrations of etonogestrel when co-administered were highest with etonogestrel/ritonavir-boosted-atazanavir (604 pg/mL) and etonogestrel/ritonavir-boosted-lopinavir (428 pg/mL), and lowest with etonogestrel/efavirenz (125 pg/mL); p < 0.001. Minimum concentration (Cmin) of ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were lower after etonogestrel implant insertion, but overall exposure, predose concentrations, clearance, and half-lives were unchanged. We found no significant change in efavirenz exposure after etonogestrel insertion.ConclusionsUnlike efavirenz, ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were not associated with significant decreases in etonogestrel concentrations. Efavirenz was associated with a significant decrease in etonogestrel concentrations.ImplicationsThe findings demonstrate no interactions between etonogestrel and ritonavir-boosted-lopinavir or ritonavir-boosted-atazanavir, but confirm the decreased efficacy of etonogestrel with efavirenz-based antiretrovirals. This information should be used to counsel women with HIV who desire long-acting reversible contraceptives.
Databáze: OpenAIRE
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