The Impact of ART on the Efficacy of Vaginally Delivered Hormonal Contraception

The Lancet HIV, September 2019

ACTG Changes Guidelines
Effective family planning, which often involves the use of hormonal contraception, is an important component of care for women living with HIV. Unfortunately, some hormones have drug interactions with some antiretrovirals that may jeopardize hormone effectiveness or tolerability. Non-orally administered hormones may reduce the risk of these drug-drug interactions. The A5316 team sought to determine whether estrogen and progestin administered by a vaginal ring would be affected by oral ART containing either efavirenz or atazanavir/ritonavir.
Overall, 84 women participated in A5316 across 21 ACTG and IMPAACT sites in Asia, South America, sub-Saharan Africa, and the United States. The woman were either not yet on ART or were receiving ART containing efavirenz- or atazanavir/ritonavir, and agreed to use a vaginal ring containing ethinyl estradiol and etonogestrel continuously over 3 weeks. The results showed that hormone concentrations were significantly changed by both types of ART. Efavirenz-based ART decreased both ethinyl estradiol and etonogestrel hormones, raising concerns for lack of efficacy and the risk of unintended pregnancies. While the atazanavir/ritonavir-based ART increased progestin exposure (providing reassurance that the contraceptive effectiveness would be maintained), it decreased estrogen exposure, which may increase the risk of mid-cycle bleeding.
While the findings are directionally similar to what we’ve seen with ART and oral hormones to date, the vaginal ring ART-hormone interaction often resulted in even larger changes in hormone exposure. A5316 further identified the influence of participant pharmacogenetics on the extent of the drug interaction. The study finding that efavirenz-based ART may jeopardize the effectiveness of hormonal contraception delivered by a vaginal ring has already been included in both the Adult and Adolescent as well as the Perinatal DHHS HIV treatment guidelines, highlighting the influence of this study. The importance of understanding the pharmacology of vaginally administered drugs has particular relevance as vaginal rings are being developed for multipurpose prevention of both HIV and pregnancy.

Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study