title: Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants: A Systematic Review and Meta-Analysis.
abstract: There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants.
  
  
  
  We conducted a systematic review of studies published between January 1980 and January 2017 that compared adverse outcomes in HIV-infected women receiving TDF- vs. non-TDF-based ART during pregnancy. The risk ratio (RR) for associations was pooled using a fixed-effects model.
  
  
  
  Seventeen studies met the study inclusion criteria. We found that the rate of preterm (<37 weeks gestation) delivery (RR = 0.90, 95% confidence interval [CI]: 0.81 to 0.99, I = 59%) and stillbirth (RR = 0.60, 95% CI: 0.43 to 0.84, I = 72.0%) were significantly lower in women exposed (vs. not) to TDF-based ART regimen. We found no increased risk in maternal severe (grade 3) or potentially life-threatening (grade 4) adverse events (RR = 0.62; 95% CI: 0.30 to 1.29), miscarriage (RR = 1.09; 95% CI: 0.80 to 1.48), very preterm (<34 weeks gestation) delivery (RR = 1.08, 95% CI: 0.72 to 1.62), small for gestational age (RR = 0.87, 95% CI: 0.67 to 1.13), low birth weight (RR = 0.91; 95% CI: 0.80 to 1.04), very low birth weight (RR = 3.18; 95% CI: 0.65 to 15.63), congenital anomalies (RR = 1.03; 95% CI: 0.83 to 1.28), infant adverse outcomes or infant mortality (age >14 days) (RR = 0.65; 95% CI: 0.23 to 1.85), but increased neonatal mortality (age <14 days) risk (RR = 5.64, 95% CI: 1.70 to 18.79) with TDR-based ART exposure. No differences were found for anthropomorphic parameters at birth; one study reported minor differences in z-scores for length and head circumference at age 1 year.
  
  
  
  TDF-based ART in pregnancy seems generally safe for women and their infants. However, data remain limited and further studies are needed, particularly to assess neonatal mortality and infant growth/bone effects.
authors.affiliation: *Departments of Epidemiology, Microbiology and Infectious Diseases, University of Pittsburgh, Pittsburgh, PA; †Department of Medicine, Centre for Infectious Diseases, Stellenbosch University, Cape Town, South Africa; ‡Departments of Epidemiology and International Health, Johns Hopkins University, Baltimore, MD; §Centre for Applied Health Research & Delivery, Warwick Medical School, The University of Warwick, Coventry, United Kingdom; ‖Department of Public Health (IHCAR), Karolinska Institute, Stockholm, Sweden; ¶Department of Global Health, Centre for Evidence-Based Health Care, Stellenbosch University, Tygerberg, South Africa; #Elizabeth Glazer Pediatric AIDS Foundation, Washington, DC; **Department of Obstetrics and Gynecology, Johns Hopkins School of Medicine, Baltimore, MD; ††Department of Statistics, University of British Columbia, Vancouver, Canada; ‡‡Global Evaluative Science, Vancouver, Canada; and §§Department of HIV, World Health Organization, Geneva, Switzerland.
authors.forename: Jean B
authors.initials: JB
authors.lastname: Nachega
authors.forename: Olalekan A
authors.initials: OA
authors.lastname: Uthman
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Jean R
authors.initials: JR
authors.lastname: Anderson
authors.forename: Steve
authors.initials: S
authors.lastname: Kanters
authors.forename: Francoise
authors.initials: F
authors.lastname: Renaud
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
authors.forename: Shaffiq
authors.initials: S
authors.lastname: Essajee
authors.forename: Meg C
authors.initials: MC
authors.lastname: Doherty
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Mills
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001724:Birth Weight / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D061214:Patient Safety; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011256:Pregnancy Outcome; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir