Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants: A Systematic Review and Meta-Analysis

J Acquir Immune Defic Syndr. 2017 Sep 1;76(1):1-12. doi: 10.1097/QAI.0000000000001359.

Abstract

Background: There are limited data on adverse effects of tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) on pregnant women and their infants.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Birth Weight / drug effects
  • CD4 Lymphocyte Count
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / transmission
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Patient Safety*
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Pregnancy Outcome
  • Tenofovir / adverse effects*
  • Tenofovir / therapeutic use*

Substances

  • Anti-HIV Agents
  • Tenofovir