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.
To assess pregnancy incidence and outcomes among women using PrEP during the periconception period.
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.
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.
Pregnancy incidence, birth outcomes (pregnancy loss, preterm birth, congenital anomalies), infant growth.
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 becoming pregnant. (ClinicalTrials.gov number, NCT00557245)