title: Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00557245.
authors.affiliation: Department of Global Health, University of Washington, Seattle2Centre for Clinical Research Kenya Medical Research Institute, Nairobi, Kenya3Department of Obstetrics and Gynaecology, Kenyatta National Hospital, Nairobi, Kenya.
authors.forename: Nelly R
authors.initials: NR
authors.lastname: Mugo
authors.affiliation: Department of Global Health, University of Washington, Seattle.
authors.forename: Ting
authors.initials: T
authors.lastname: Hong
authors.affiliation: Department of Global Health, University of Washington, Seattle4Department of Medicine, University of Washington, Seattle5Department of Epidemiology, University of Washington, Seattle.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.affiliation: Department of Global Health, University of Washington, Seattle6Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.affiliation: Department of Global Health, University of Washington, Seattle7Department of Obstetrics and Gynecology, University of Washington, Seattle8Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bukusi
authors.affiliation: Department of Global Health, University of Washington, Seattle4Department of Medicine, University of Washington, Seattle5Department of Epidemiology, University of Washington, Seattle9Department of Pediatrics, University of Washington, Seattle.
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
authors.affiliation: The AIDS Support Organization (TASO), Kampala, Uganda.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wangisi
authors.affiliation: Department of Reproductive Health, Moi University, Eldoret, Kenya.
authors.forename: Edwin
authors.initials: E
authors.lastname: Were
authors.affiliation: Department of Global Health, University of Washington, Seattle.
authors.forename: Renee
authors.initials: R
authors.lastname: Heffron
authors.affiliation: Division of Infectious Disease, Massachusetts General Hospital, Boston13Center for Global Health, Massachusetts General Hospital, Boston.
authors.forename: Lynn T
authors.initials: LT
authors.lastname: Matthews
authors.affiliation: Department of Global Health, University of Washington, Seattle.
authors.forename: Susan
authors.initials: S
authors.lastname: Morrison
authors.affiliation: Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ngure
authors.affiliation: Department of Global Health, University of Washington, Seattle4Department of Medicine, University of Washington, Seattle5Department of Epidemiology, University of Washington, Seattle.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
mesh_terms: D000022:Abortion, Spontaneous; D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002657:Child Development; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005191:Family Characteristics; D005260:Female; D005306:Fertilization; D015658:HIV Infections / Q000517:prevention & control*; D020010:Heterosexuality; D006801:Humans; D007231:Infant, Newborn; D007630:Kenya; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D011256:Pregnancy Outcome; D011295:Prenatal Care; D000068698:Tenofovir; D014454:Uganda
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine