Phosphaturia in HIV-Exposed Uninfected Neonates Associated with Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy
Author:
Purswani Murli U1ORCID, Jacobson Denise L2, DiMeglio Linda A3, Yao Tzy-Jyun2, Kopp Jeffrey B4, Van Dyke Russell B5, Yu Wendy2, Siberry George K6ORCID, , Chadwick Ellen, Sanders Margaret Ann, Malee Kathleen, Pyun Yoonsun, Paul Mary, Buschur Shelley, McMullen-Jackson Chivon, Harris Lynnette, Purswani Murli, Alvarado Marvin, Baig Mahoobullah Mirza, Villegas Alma, Robinson Lisa-Gaye, Blood James, Garvie Patricia, Cooley Dia, Borkowsky William, Deygoo Nagamah Sandra, Lewis Jennifer, Dieudonne Arry, Bettica Linda, Johnson Juliette, Surowiec Karen, Knapp Katherine, Russell-Bell Jamie, Wilkins Megan, Love Stephanie, Rosario Nicolas, Angeli-Nieves Lourdes, Olivera Vivian, Kohlhoff Stephan, Dennie Ava, Kaye Jean, Wallier Jenny, Silio Margarita, Craig Karen, Sirois Patricia, Hutto Cecelia, Hickman Paige, Huldtquist Julie, Marullo Dan, Spector Stephen A, Figueroa Veronica, Loughran Megan, Nichols Sharon, McFarland Elizabeth, Kwon Christine, Chambers Carrie, Rathore Mobeen, Tejan Jamilah, Borestil Beatrice, Routman Staci, Scott Gwendolyn, Gil Gustavo, Fernandez Gabriel, Cuadra Anai, Frederick Toni, Davtyan Mariam, Morales-Avendano Guadalupe, Rodriguez Zoe M, Torres Lizmarie, Scalley Nydia
Affiliation:
1. Division of Pediatric Infectious Disease, BronxCare Health System, Icahn School of Medicine at Mount Sinai , Bronx, New York , USA 2. Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health , Boston, Massachusetts , USA 3. Division of Pediatric Endocrinology and Diabetology, Riley Hospital for Children at IU Health, Indiana University School of Medicine , Indianapolis, Indiana , USA 4. Kidney Disease Section, NIDDK, NIH , Bethesda, Maryland , USA 5. Section of Pediatric Infectious Diseases, Tulane University School of Medicine , New Orleans, Louisiana , USA 6. Prevention Care and Treatment Division, Office of HIV/AIDS, United States Agency for International Development , Washington, District of Columbia , USA
Abstract
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.
Publisher
Oxford University Press (OUP)
|
|