Pregnancy Incidence and Outcomes Among Women Receiving Preexposure Prophylaxis for HIV Prevention

Abstract

Importance Antiretroviral pre-exposure prophylaxis (PrEP), using tenofovir disoproxil fumarate and combination tenofovir disoproxil fumarate / emtricitabine, is efficacious for prevention of HIV acquisition. PrEP could reduce periconception HIV risk, but the effect on pregnancy outcomes is not well defined. Objective To assess pregnancy incidence and outcomes among women using PrEP during the periconception period. Design Randomized trial among 1785 HIV serodiscordant heterosexual couples (the Partners PrEP Study) in which the female partner was HIV uninfected that demonstrated that PrEP was efficacious for HIV prevention, conducted between July 2008 and June 2013 at 9 sites in Kenya and Uganda. Intervention Daily oral tenofovir disoproxil fumarate (TDF) (n=598), combination tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) (n=566), or placebo (n=621) through July 2011, when PrEP demonstrated efficacy for HIV prevention; thereafter, participants continued receiving active PrEP, without placebo. Pregnancy testing occurred monthly and study medication was discontinued upon pregnancy detection. Main Outcomes Pregnancy incidence, birth outcomes (pregnancy loss, preterm birth, congenital anomalies), infant growth. Results A total of 431 pregnancies occurred. Pregnancy incidence was 10.0 per 100 person-years among women assigned placebo, 11.9 among those assigned TDF (incidence difference 1.9, 95% confidence interval [CI] −1.1–4.9, p=0.22 versus placebo), and 8.8 among those assigned TDF-FTC (incidence difference −1.3, 95% CI −4.1–1.5, p=0.39 versus placebo). Prior to discontinuation of the placebo treatment group in July 2011, the occurrence of pregnancy loss (96 of 288 pregnancies), was 42.5% for women receiving TDF-FTC compared with 32.3% for those receiving placebo (difference for TDF-FTC versus placebo 10.2%, 95% CI −5.3–25.7, p=0.16) and was 27.7% for those receiving TDF alone (difference versus placebo −4.6%, 95% CI −18.1–8.9, p=0.46). After July 2011, the frequency of pregnancy loss (52 of 143 pregnancies) was 37.5% for TDF-FTC and 36.7% for TDF alone (difference 0.8%, 95% CI −16.8–18.5, p=0.92). Preterm birth and congenital anomalies did not differ significantly for those who received PrEP versus placebo. Infants born to women randomized to PrEP had growth throughout the first year of life not statistically different than placebo and with point estimates that did not suggest growth restriction. Conclusions and Relevance Among HIV serodiscordant heterosexual African couples, differences in pregnancy incidence, birth outcomes, and infant growth were not statistically different for women receiving PrEP with TDF alone or combination TDF-FTC compared to placebo at the time of conception. Given that PrEP was discontinued when pregnancy was detected and that confidence intervals for the birth outcomes were wide, definitive statements about safety of PrEP in the periconception period cannot be made. These results should be discussed with HIV uninfected women receiving PrEP who are considering bec...

Response to “Oral PrEP for young African women and men”

“…The high viral loads that occur during acute HIV infection significantly increase the risk of HIV transmission to the foetus. PrEP substantially reduces the risk of women becoming HIV-positive, and appears safe during early pregnancy per the Partners PrEP Study [1]. Additional safety data on infant and pregnancy outcomes will be obtained from ongoing PrEP implementation projects among women who are counselled about PrEP effectiveness and available safety data, and choose to continue PrEP throughout their pregnancy.…”

Fertility-related research needs among women at the margins

“…Findings from pregnancy outcomes among women conceiving on PrEP and/or microbicides during trials have provided little reason for concern; however, in all these trials study drug has been stopped once pregnancy was detected. [47][48][49][50][51][52][53] Overall, these evidence gaps reflect the only recently expanded HIV prevention options for HIV-affected couples, but also reflect years of stigma, discrimination and lack of legal protection for the reproductive rights of HIV-affected couples.…”

Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention

“…In the Partners PrEP Study, among 288 women with first trimester (median= 35 days) TDF exposure 49 , the frequency of pregnancy loss was 42.5% for women receiving FTC-TDF (p= 0.46) and 27.7% on TDF alone (p=0.16) vs 32.3% on placebo. In addition, there were no significant differences in pregnancy-related and infant adverse outcomes including preterm birth, congenital anomalies, and growth throughout the first year of life for infants born to women who received PrEP vs placebo.…”