[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Investigation
July 23/30, 2014

Pregnancy Incidence and Outcomes Among Women Receiving Preexposure Prophylaxis for HIV Prevention: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Global Health, University of Washington, Seattle
  • 2Centre for Clinical Research Kenya Medical Research Institute, Nairobi, Kenya
  • 3Department of Obstetrics and Gynaecology, Kenyatta National Hospital, Nairobi, Kenya
  • 4Department of Medicine, University of Washington, Seattle
  • 5Department of Epidemiology, University of Washington, Seattle
  • 6Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 7Department of Obstetrics and Gynecology, University of Washington, Seattle
  • 8Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
  • 9Department of Pediatrics, University of Washington, Seattle
  • 10The AIDS Support Organization (TASO), Kampala, Uganda
  • 11Department of Reproductive Health, Moi University, Eldoret, Kenya
  • 12Division of Infectious Disease, Massachusetts General Hospital, Boston
  • 13Center for Global Health, Massachusetts General Hospital, Boston
  • 14Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
JAMA. 2014;312(4):362-371. doi:10.1001/jama.2014.8735

Importance  Antiretroviral preexposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF) and combination emtricitabine/tenofovir disoproxil fumarate (FTC+TDF), is efficacious for prevention of human immunodeficiency virus (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, Setting, and Participants  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.

Interventions  Daily oral TDF (n = 598), combination FTC+TDF (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 when pregnancy was detected.

Main Outcomes and Measures  Pregnancy incidence, birth outcomes (live births, pregnancy loss, preterm birth, congenital anomalies), and 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% CI, −1.1 to 4.9 [P = .22 vs placebo]), and 8.8 among those assigned FTC+TDF (incidence difference, −1.3; 95% CI, −4.1 to 1.5 [P = .39 vs placebo]). Before discontinuation of the placebo treatment group in July 2011, the occurrence of pregnancy loss (96 of 288 pregnancies) was 42.5% for women receiving FTC+TDF compared with 32.3% for those receiving placebo (difference for FTC+TDF vs placebo, 10.2%; 95% CI, −5.3% to 25.7%; P = .16) and was 27.7% for those receiving TDF alone (difference vs placebo, −4.6%; 95% CI, −18.1% to 8.9%; P = .46). After July 2011, the frequency of pregnancy loss (52 of 143 pregnancies) was 37.5% for FTC+TDF and 36.7% for TDF alone (difference, 0.8%; 95% CI, −16.8% to 18.5%; P = .92). Occurrence of preterm birth, congenital anomalies, and growth throughout the first year of life did not differ significantly for infants born to women who received PrEP vs placebo.

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 FTC+TDF compared with placebo at conception. Given that PrEP was discontinued when pregnancy was detected and that CIs for the birth outcomes were wide, definitive statements about the 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.

Trial Registration  clinicaltrials.gov Identifier: NCT00557245