Abstract
Background: Tenofovir disoproxil fumarate (TDF) is often used in treating pregnant women living with HIV. Third-trimester TDF exposure is associated with a 12% reduction in bone mineral content in HIV-exposed uninfected (HEU) neonates. The potential mechanisms underlying this observation are unknown. Methods: The TDF study enrolled newborns of gestational age ≥36 weeks from the Surveillance Monitoring for Antiretroviral Therapy and Toxicities study based on in utero TDF exposure (TDF use ≥8 weeks in the third trimester vs none). Blood and urine samples were collected cross-sectionally within 30 days of birth to assess renal function (serum creatinine, serum phosphate, eGFR, percent tubular reabsorption of phosphate [PTRP]), and bone turnover (serum parathyroid hormone, 25-OH vitamin D [25(OH)D], and urinary cross-linked N-telopeptide of type 1 collagen). For each biomarker, a LOESS plot was fit using values at age at specimen collection; regression lines over age were fit among samples collected from 4 to 30 days, to compare slopes by TDF exposure. Results: Among 141 neonates, 77 were TDF-exposed and 64 TDF-unexposed. Between age 4 and 30 days, PTRP decreased more rapidly in the TDF-exposed compared to the unexposed group with slopes of -0.58 vs -0.08/day (difference -0.50/day [95% CI -0.88, -0.11]). Slopes for 25(OH)D were similar in both groups, but serum levels were lower in TDF-exposed neonates (median [IQR]: 22 [19, 29] vs 26 [22, 37] ng/mL). No differences were observed for other biomarkers. Conclusions: Third-trimester in utero exposure to TDF is associated with increased urinary loss of phosphate and lower serum concentrations of 25(OH)D in HEU neonates.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 396-405 |
| Number of pages | 10 |
| Journal | Journal of the Pediatric Infectious Diseases Society |
| Volume | 13 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2024 |
Funding
This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development, Office of the Director, National Institutes of Health, National Institute of Dental and Craniofacial Research, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Deafness and Other Communication Disorders, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Alcohol Abuse and Alcoholism, and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (grant number HD052102) (Principal Investigator: George R Seage III; Program Director: Liz Salomon) and the Tulane University School of Medicine (grant number HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis), and through Harvard T.H. Chan School of Public Health for the Pediatric HIV/AIDS Cohort Study 2020 (grant number P01HD103133) (Multiple Principal Investigators: Ellen Chadwick, Sonia Hernandez-Diaz, Jennifer Jao, Paige Williams; Program Director: Liz Salomon). Data management services were provided by Frontier Science (Data Management Center Director: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc. (Project Directors: Julie Davidson, Tracy Wolbach). Jeffrey Kopp is supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases. The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the United States Agency for International Development, National Institutes of Health, or U.S. Department of Health and Human Services. Financial support. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development, Office of the Director, National Institutes of Health, National Institute of Dental and Craniofacial Research, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute on Deafness and Other Communication Disorders, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Alcohol Abuse and Alcoholism, and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (grant number HD052102) (Principal Investigator: George R Seage III; Program Director: Liz Salomon) and the Tulane University School of Medicine (grant number HD052104) (Principal Investigator: Russell Van Dyke*; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis), and through Harvard T.H. Chan School of Public Health for the Pediatric HIV/AIDS Cohort Study 2020 (grant number P01HD103133) (Multiple Principal Investigators: Ellen Chadwick, Sonia Hernandez-Diaz, Jennifer Jao, Paige Williams; Program Director: Liz Salomon). Data management services were provided by Frontier Science (Data Management Center Director: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc. (Project Directors: Julie Davidson, Tracy Wolbach). Jeffrey Kopp is supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases. The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the United States Agency for International Development, National Institutes of Health, or U.S. Department of Health and Human Services.
Keywords
- 25-OH vitamin D
- HEU
- TDF
- in utero exposure
- percent tubular reabsorption of phosphate
- renal
ASJC Scopus subject areas
- General Medicine
