Maternal tenofovir disoproxil fumarate (TDF) treatment among HIV-infected pregnant women results in fetal tenofovir (TFV) exposure. Fetal TFV toxicity was demonstrated in animals, but most clinical investigations have not observed toxicity in humans.
We evaluated HIV-exposed, uninfected infants in the Surveillance Monitoring for Antiretroviral Therapy Toxicities cohort of the Pediatric HIV/AIDS Cohort Study whose mothers were prescribed TDF for ≥8 third trimester weeks. Infant dual-energy X-ray absorptiometry scans were obtained at 0–4 weeks to measure whole body bone mineral content. Meconium TFV concentrations were quantified by liquid chromatography–tandem mass spectrometry.
Fifty-eight TFV-exposed infants had meconium TFV quantified. Detectable concentrations were 11–48,100 ng/g; 3 infants had undetectable concentrations. Maternal TDF prescription duration ranged from 8 to 41 gestational weeks; infant gestational ages were 36–41 weeks. Meconium TFV concentrations were not correlated with TFV exposure duration or timing and did not vary by concomitant prescription of protease inhibitors. Increased meconium TFV concentrations were associated with greater gestational ages (ρ = 0.29, P = 0.03) and lower maternal plasma HIV RNA before delivery (ρ = −0.29, P = 0.04). Meconium TFV concentrations were not associated with infant weight, length (n = 58) or bone mineral content (n = 49).
For the first time, we explored associations between meconium TFV concentrations and infant growth and bone measurements; we did not observe a meconium concentration-dependent relationship for these infant outcomes. These findings support other clinical research failing to show dose–response relationships for growth and bone outcomes among intrauterine TFV-exposed infants. High meconium TFV concentrations correlated with low maternal viral load, suggesting maternal TDF adherence significantly contributes to meconium TFV concentrations.
From the *Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland; †Department of Epidemiology, ‡Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts; §Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; ¶Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana; and ‖Pediatrics Department, University of Illinois at Chicago, Chicago, Illinois.
Accepted for publication April 20, 2015.
The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard University School of Public Health (HD052102, 3 U01 HD052102-05S1, 3 U01 HD052102-06S3; principal investigator: George Seage; project director: Julie Alperen) and the Tulane University School of Medicine (HD052104, 3U01HD052104-06S1; principal investigator: Russell Van Dyke; co-principal investigator: Kenneth Rich; project director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson). The authors have no other funding or conflicts of interest to disclose. The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or U.S. Department of Health and Human Services.
Address for correspondence: Marilyn A. Huestis, PhD, Chemistry and Drug Metabolism, IRP, NIDA, NIH, 251 Bayview Blvd, Suite 200, Rm 05A721, Baltimore, MD 21224. E-mail: email@example.com.