Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy

Clin Infect Dis. 2015 Sep 15;61(6):996-1003. doi: 10.1093/cid/civ437. Epub 2015 Jun 9.


Background: Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero.

Methods: We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates.

Results: Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants.

Conclusions: Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies.

Clinical trials registration: ClinicalTrials.gov NCT01310023.

Keywords: HIV; infant bone mineral content; intrauterine exposure; tenofovir.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Bone Density*
  • Cross-Sectional Studies
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Infant, Newborn
  • Maternal Exposure*
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Tenofovir / adverse effects*
  • Tenofovir / therapeutic use
  • United States


  • Anti-HIV Agents
  • Tenofovir

Associated data

  • ClinicalTrials.gov/NCT01310023