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2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy

BACKGROUND: Our recent study showed significantly lower bone mineral content (BMC) in HIV-exposed uninfected (HEU) neonates born to HIV-infected (HIV+) mothers who took tenofovir disoproxil fumarate (TDF) in late pregnancy compared with no TDF use. In this cohort we sought to understand possible mec...

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Autores principales: Purswani, Murli, Jacobson, Denise, Kopp, Jeffrey, Dyke, Russell Van, DiMeglio, Linda, Yao, Tzy-Jyun, Miller, Tracie, Siberry, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252985/
http://dx.doi.org/10.1093/ofid/ofy210.1914
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author Purswani, Murli
Jacobson, Denise
Kopp, Jeffrey
Dyke, Russell Van
DiMeglio, Linda
Yao, Tzy-Jyun
Miller, Tracie
Siberry, George
author_facet Purswani, Murli
Jacobson, Denise
Kopp, Jeffrey
Dyke, Russell Van
DiMeglio, Linda
Yao, Tzy-Jyun
Miller, Tracie
Siberry, George
author_sort Purswani, Murli
collection PubMed
description BACKGROUND: Our recent study showed significantly lower bone mineral content (BMC) in HIV-exposed uninfected (HEU) neonates born to HIV-infected (HIV+) mothers who took tenofovir disoproxil fumarate (TDF) in late pregnancy compared with no TDF use. In this cohort we sought to understand possible mechanisms for lower BMC by comparing markers of bone metabolism and renal function with TDF exposure in HEU neonates. METHODS: Among a subset of HEU children in the multicenter (United States and Puerto Rico) observational Surveillance Monitoring for ART Toxicities (SMARTT) Cohort study, we enrolled neonates (≥36 weeks gestational age) of HIV+ mothers who took TDF for ≥8 weeks in the third trimester (TDF+) or no TDF in pregnancy (TDF-). In addition to BMC measures, we collected a blood and urine sample on each child ≤30 days of birth to measure serum creatinine, phosphate, 25-OH vitamin D, parathyroid hormone and urine creatinine, phosphate and N-terminal telopeptide. Standard equations were used to estimate proximal tubular phosphate reabsorption and glomerular filtration rate (eGFR). Comparisons were made by TDF exposure using Wilcoxon and Fisher’s exact tests. We fit linear models to compare TDF+ and TDF− for each assay by age in days at sample collection (slope), stratified by age group at sample collection time (0–3 days, 4–30 days). RESULTS: Of 160 HEU neonates (Black 71%, Hispanic 31%), 82 were TDF+ and 78 TDF−. Sociodemographic and anthropometric characteristics did not differ by TDF exposure in each age group. Within 0–3 days of life, TDF+ had a greater decline in serum creatinine (P = 0.04) and a greater increase in eGFR compared with TDF− (P = 0.06), but no difference in slope by TDF exposure within 4–30 days of life, nor in serum phosphate in either age group. Proximal tubular phosphate reabsorption was similar for both groups within the first 3 days of life, with a significantly greater decline in phosphate reabsorption between 4 and 30 days of life in the TDF+ compared with the TDF− group (P = 0.006, Figure 1). Bone markers did not differ by TDF exposure for either age group. CONCLUSION: Urinary phosphate loss was increased among HEU neonates of mothers who took TDF in late pregnancy. This suggests proximal tubular dysfunction and may explain, at least in part, the decrease in BMC previously described. [Image: see text] DISCLOSURES: R. Van Dyke, Giliad Sciences: Grant Investigator, Research grant.
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spelling pubmed-62529852018-11-28 2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy Purswani, Murli Jacobson, Denise Kopp, Jeffrey Dyke, Russell Van DiMeglio, Linda Yao, Tzy-Jyun Miller, Tracie Siberry, George Open Forum Infect Dis Abstracts BACKGROUND: Our recent study showed significantly lower bone mineral content (BMC) in HIV-exposed uninfected (HEU) neonates born to HIV-infected (HIV+) mothers who took tenofovir disoproxil fumarate (TDF) in late pregnancy compared with no TDF use. In this cohort we sought to understand possible mechanisms for lower BMC by comparing markers of bone metabolism and renal function with TDF exposure in HEU neonates. METHODS: Among a subset of HEU children in the multicenter (United States and Puerto Rico) observational Surveillance Monitoring for ART Toxicities (SMARTT) Cohort study, we enrolled neonates (≥36 weeks gestational age) of HIV+ mothers who took TDF for ≥8 weeks in the third trimester (TDF+) or no TDF in pregnancy (TDF-). In addition to BMC measures, we collected a blood and urine sample on each child ≤30 days of birth to measure serum creatinine, phosphate, 25-OH vitamin D, parathyroid hormone and urine creatinine, phosphate and N-terminal telopeptide. Standard equations were used to estimate proximal tubular phosphate reabsorption and glomerular filtration rate (eGFR). Comparisons were made by TDF exposure using Wilcoxon and Fisher’s exact tests. We fit linear models to compare TDF+ and TDF− for each assay by age in days at sample collection (slope), stratified by age group at sample collection time (0–3 days, 4–30 days). RESULTS: Of 160 HEU neonates (Black 71%, Hispanic 31%), 82 were TDF+ and 78 TDF−. Sociodemographic and anthropometric characteristics did not differ by TDF exposure in each age group. Within 0–3 days of life, TDF+ had a greater decline in serum creatinine (P = 0.04) and a greater increase in eGFR compared with TDF− (P = 0.06), but no difference in slope by TDF exposure within 4–30 days of life, nor in serum phosphate in either age group. Proximal tubular phosphate reabsorption was similar for both groups within the first 3 days of life, with a significantly greater decline in phosphate reabsorption between 4 and 30 days of life in the TDF+ compared with the TDF− group (P = 0.006, Figure 1). Bone markers did not differ by TDF exposure for either age group. CONCLUSION: Urinary phosphate loss was increased among HEU neonates of mothers who took TDF in late pregnancy. This suggests proximal tubular dysfunction and may explain, at least in part, the decrease in BMC previously described. [Image: see text] DISCLOSURES: R. Van Dyke, Giliad Sciences: Grant Investigator, Research grant. Oxford University Press 2018-11-26 /pmc/articles/PMC6252985/ http://dx.doi.org/10.1093/ofid/ofy210.1914 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Purswani, Murli
Jacobson, Denise
Kopp, Jeffrey
Dyke, Russell Van
DiMeglio, Linda
Yao, Tzy-Jyun
Miller, Tracie
Siberry, George
2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy
title 2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy
title_full 2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy
title_fullStr 2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy
title_full_unstemmed 2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy
title_short 2261. Phosphaturia in HIV-Exposed Uninfected Neonates Associated With Maternal Use of Tenofovir Disoproxil Fumarate in Late Pregnancy
title_sort 2261. phosphaturia in hiv-exposed uninfected neonates associated with maternal use of tenofovir disoproxil fumarate in late pregnancy
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252985/
http://dx.doi.org/10.1093/ofid/ofy210.1914
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