Dapivirine Vaginal Ring Use Does Not Diminish the Effectiveness of Hormonal Contraception

Jennifer E. Balkus, PhD, MPH; Thesla Palanee-Phillips, PhD; Krishnaveni Reddy, MBChB; Samantha Siva, MBChB; Ishana Harkoo, MBChB; Clemensia Nakabiito, MBChB; Kenneth Kintu, MBChB; Gonasangrie Nair, MBChB; Catherine Chappell, MD; Flavia Matovu Kiweewa, MBChB; Samuel Kabwigu, MBChB; Logashvari Naidoo, MBChB; Nitesha Jeenarain, MBChB; Mark Marzinke, PhD; Lydia Soto-Torres, MD; Elizabeth R. Brown, ScD; Jared M. Baeten, MD, PhD

Disclosures

J Acquir Immune Defic Syndr. 2017;76(2):e47-e51. 

In This Article

Abstract and Introduction

Abstract

Objective: To evaluate the potential for a clinically relevant drug–drug interaction with concomitant use of a dapivirine vaginal ring, a novel antiretroviral-based HIV-1 prevention strategy, and hormonal contraception by examining contraceptive efficacies with and without dapivirine ring use.

Design: A secondary analysis of women participating in MTN-020/ASPIRE, a randomized, double-blind, placebo-controlled trial of the dapivirine vaginal ring for HIV-1 prevention.

Methods: Use of a highly effective method of contraception was an eligibility criterion for study participation. Urine pregnancy tests were performed monthly. Pregnancy incidence by arm was calculated separately for each hormonal contraceptive method and compared using an Andersen–Gill proportional hazards model stratified by site and censored at HIV-1 infection.

Results: Of 2629 women enrolled, 2310 women returned for follow-up and reported using a hormonal contraceptive method at any point during study participation (1139 in the dapivirine arm and 1171 in the placebo arm). Pregnancy incidence in the dapivirine arm versus placebo among women using injectable depot medroxyprogesterone acetate was 0.43% vs. 0.54%, among women using injectable norethisterone enanthate was 1.15% vs. 0%, among women using hormonal implants was 0.22% vs. 0.69%, and among women using oral contraceptive pills was 32.26% vs. 28.01%. Pregnancy incidence did not differ by study arm for any of the hormonal contraceptive methods.

Conclusions: Use of the dapivirine ring does not reduce the effectiveness of hormonal contraceptives for pregnancy prevention. Oral contraceptive pill use was associated with high pregnancy incidence, potentially because of poor pill adherence. Injectable and implantable methods were highly effective in preventing pregnancy.

Introduction

Prevention of HIV-1 and unplanned pregnancy are global public health priorities for reproductive-aged women.[1] For women with or at risk of HIV-1, concurrent use of hormonal contraceptives for pregnancy prevention and antiretrovirals for HIV-1 treatment or prevention could result in potential drug–drug interactions that may diminish contraceptive effectiveness.[2,3] Contraceptive hormones are metabolized by hepatic cytochrome P450 enzymes, and certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) can induce cytochrome P450 enzymes leading to reduced plasma progestin concentrations, with some NNRTIs having a greater impact on progestin pharmacokinetics than others.[4–8] Among HIV-1–infected women, use of the NNRTI efavirenz as part of combination HIV-1 treatment has been associated with a reduced effectiveness of contraceptive implants.[3,6,7,9]

A vaginal ring containing dapivirine, a novel NNRTI, demonstrated effectiveness for HIV-1 prevention,[10,11] with HIV-1 incidence reduced in 2 randomized trials by approximately one-third overall and by >50% among those with biologic evidence of ring use.[11,12] Pregnancy incidence and outcomes did not differ between those receiving active dapivirine vaginal ring and placebo;[13] however, the potential for a clinically relevant drug–drug interaction between vaginally delivered dapivirine and hormonal contraceptive effectiveness has not been assessed in epidemiologic studies. Among women who participated in a phase III trial of the dapivirine vaginal ring, we compared the incidence of pregnancy in women randomized with the dapivirine ring versus placebo, stratified by hormonal contraceptive method.

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