The dapivirine vaginal ring has been shown to be safe and effective for HIV prevention. Understanding the safety of exposure during pregnancy is important for the potential roll-out of the dapivirine ring among reproductive aged women. In the MTN-020/ASPIRE trial, use of a highly effective contraceptive method was a criterion for study participation and a range of methods were offered to study participants. However, pregnancies did occur, resulting in short-term exposure to study product during the periconception period. This analysis assessed pregnancy incidence and outcomes among women randomized to receive the dapivirine ring versus matching placebo.
ASPIRE was a randomized, double-blind, placebo-controlled phase III safety and effectiveness study of the dapivirine vaginal ring for HIV-1 prevention. Sexually active women aged 18-45 from Malawi, South Africa, Uganda, and Zimbabwe were enrolled. Pregnancy tests were performed monthly and, if positive, study product was withheld during pregnancy and breastfeeding. Pregnancy incidence by arm was calculated and compared using an Andersen-Gill proportional hazards model with censoring at HIV infection. Pregnancy outcomes and infant congenital anomalies were determined by participant report and medical record review.
Of 2629 women enrolled, 78 reported prior history of tubal ligation, leaving 2551 women for analysis. A total of 179 pregnancies were detected in 169 women, resulting in 180 pregnancy outcomes (86 in the dapivirine arm and 94 in the placebo arm). Pregnancy incidence in the dapivirine arm was 4.0 per 100 person-years (95% CI 3.1-5.1) versus 4.3 per 100 person-years (95% CI 3.4-5.5) in the placebo arm (HR=0.93, 95% CI 0.68-1.26). Pregnancy outcomes were similar by arm (see Table). Among 114 pregnancies that resulted in live births, data on potential congenital anomalies were available for 107, with any anomaly seen in 4 (8%) in the dapivirine arm versus 4 (7%) in the placebo arm and no pattern of anomalies for those assigned dapivirine.
Pregnancy rates did not differ between women randomized to dapivirine ring versus placebo in the ASPIRE trial. Pregnancy outcomes and the frequency of site-identified congenital anomalies were also similar by arm, suggesting that dapivirine use in the periconception period is not associated with adverse effects on pregnancy. Additional studies are needed to further assess the safety of the dapivirine ring use throughout pregnancy.