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

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

George K Siberry  1 , Denise L Jacobson  2 , Heidi J Kalkwarf  3 , Julia W Wu  4 , Linda A DiMeglio  5 , Ram Yogev  6 , Katherine M Knapp  7 , Justin J Wheeler  8 , Laurie Butler  9 , Rohan Hazra  1 , Tracie L Miller  10 , George R Seage 3rd  4 , Russell B Van Dyke  11 , Emily Barr  12 , Mariam Davtyan  13 , Lynne M Mofenson  1 , Kenneth C Rich  14 ; Pediatric HIV/AIDS Cohort Study
Collaborators, Affiliations

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

George K Siberry et al. Clin Infect Dis. .

Abstract

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.

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Figures

Figure 1.
Figure 1.
Participants were enrolled 2 April 2011 to 4 June 2013 during pregnancy (gestation age ≥23 weeks) through 2 weeks after birth. Eligibility was confirmed at birth for those enrolled before birth; 21 infants were excluded for the following reasons: gestational age less than 36 weeks (N = 16, 1 of whom was fetal demise), born at another hospital (N = 1), stillborn (N = 1), mother lost custody of child (N = 1), disqualifying change in maternal antiretroviral regimen during pregnancy (N = 2). Abbreviations: DXA, dual-energy X-ray absorptiometry; TDF, tenofovir disoproxil fumarate.
See this image and copyright information in PMC

Comment in

  • Reply to Koo et al.
    Siberry GK, Jacobson DL; for coauthors and the Pediatric HIV/AIDS Cohort Study. Siberry GK, et al. Clin Infect Dis. 2016 May 15;62(10):1324-5. doi: 10.1093/cid/ciw116. Epub 2016 Mar 1. Clin Infect Dis. 2016. PMID: 26936672 Free PMC article. No abstract available.
  • Bone Mineral Content in Neonates.
    Koo W, Caldito G, Bocchini J Jr. Koo W, et al. Clin Infect Dis. 2016 May 15;62(10):1323-4. doi: 10.1093/cid/ciw115. Epub 2016 Mar 1. Clin Infect Dis. 2016. PMID: 26936674 No abstract available.

References

    1. World Health Organization consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach, 2013. Available at: http://www.who.int/hiv/pub/guidelines/arv2013/download/en/. Accessed 15 March 2015. - PubMed
    1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services; Available at: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed 15 March 2015.
    1. Gallant JE, Staszewski S, Pozniak AL et al. . Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004; 292:191–201. - PubMed
    1. Stellbrink H-J, Orkin C, Arribas JR et al. . Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study . Clin Infect Dis 2010; 51:963–72. - PubMed
    1. McComsey GA, Kitch D, Daar ES et al. . Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: AIDS Clinical Trials Group A5224s, a Substudy of ACTG A5202. J Infect Dis 2011; 203:1791–801. - PMC - PubMed

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