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  Conference on Retroviruses
and Opportunistic Infections (CROI)
Boston, Massachusetts
March 4-7, 2018
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EFV and ATV/r "Profoundly Alter" Levels of Vaginal Ring Hormonal Contraceptives
25th Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2018, Boston
Mark Mascolini
Efavirenz or atazanavir/ritonavir greatly raised or lowered levels of the contraceptives etonogestrel (ENG) and ethinyl estradiol (EE) delivered together by vaginal ring to women with HIV [1]. The findings may require action by women using a hormonal ring with efavirenz.
Contraception remains essential to many women with HIV who wish to prevent unintended pregnancies. Vaginal ring contraceptives offer the convenience of stable systemic hormone delivery over 21 days at concentrations lower than those provided by oral or injectable contraceptives. Drug-drug interactions between antiretrovirals and hormonal contraceptives are much studied, but the impact of antiretrovirals on hormonal agents released by vaginal rings remains unknown.
To address this question, AIDS Clinical Trials Group (ACTG) investigators analyzed ENG and EE levels in HIV-positive women taking efavirenz or atazanavir/ritonavir, comparing findings with levels in women who had not started antiretroviral therapy. ACTG A5316 was an international pharmacokinetic study of women 16 years old or older and willing to use a second, nonhormonal form of contraception [2]. Women not taking antiretrovirals had a CD4 count of at least 350. Antiretroviral-treated women took their regimen for at least 30 days and had a viral load below 400 copies. No one could be taking other hormonal therapies or agents that may interact with study drugs.
Women inserted a vaginal ring containing ENG/EE at a dose of 120/15 mcg/day. Twenty-seven took no antiretrovirals, 28 took 600 mg of efavirenz daily, and 29 took 300/100 mg of atazanavir/ritonavir. Health workers collected samples to measure plasma concentrations of ENG and EE 7, 14, and 21 days after ring insertion. The PK analysis included 25 untreated women, 25 taking efavirenz, and 24 taking atazanavir/ritonavir.
Of the 74 women, 33 lived in North America, 21 in South America, 12 in Africa, and 8 in Asia. Across the three study groups, 42% to 64% of women were black, 32% to 40% Hispanic, 12% to 21% Asian, and 4% white. Body mass index averaged about 26 kg/m2 across the three groups. Antiretroviral-treated women had a median viral load of 40 copies and untreated women had a median load of 2100 copies.
Vaginal rings were safe in this study, and women tolerated them well. Compared with antiretroviral-naive women, those taking efavirenz had 53% to 57% lower plasma levels of EE from day 7 to day 21 and those taking atazanavir/ritonavir had 29% to 35% lower EE concentrations. Compared with the antiretroviral-naive group, women taking efavirenz had 76% to 79% lower ENG exposure in plasma and those taking atazanavir/ritonavir had 71% to 79% higher ENG exposure.
The researchers concluded that atazanavir/ritonavir "is unlikely to impact the effectiveness of vaginal ring contraceptives." But they cautioned that efavirenz-based therapy may lower the effectiveness of vaginal ring contraceptives. That might prompt clinicians to recommend switching contraceptive methods or adding a barrier method to the vaginal ring until the clinical import of these findings becomes clear. The ACTG team believes the findings "highlight the importance of having a range of contraceptive method options and ART strategies for women living with HIV" to ensure optimal efficacy.
1. Scarsi KK, Cramer YS, Gingrich D, et al. Vaginal contraceptive hormone exposure profoundly altered by EFV- and ATV/r-based ART. 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 141. 2. ClinicalTrials.gov. Evaluating pharmacokinetic interactions with vaginal ring contraceptives and ART. ClinicalTrials.gov identifier NCT01903031. https://clinicaltrials.gov/ct2/show/NCT01903031