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The effects of maternal tenofovir disoproxil fumarate-emtricitabine-efavirenz treatment on the growth of breast feeding infants

Dissertation (MSc)--University of Pretoria, 2025.

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Other Authors: Outhoff, Kim
Format: Thesis
Language:English
Published: University of Pretoria 2025
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author2 Outhoff, Kim
author_browse Outhoff, Kim
author_facet Outhoff, Kim
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dc_rights_str_mv © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.
description Dissertation (MSc)--University of Pretoria, 2025.
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institution University of Pretoria (South Africa)
language English
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spelling oai:repository.up.ac.za:2263/101286 The effects of maternal tenofovir disoproxil fumarate-emtricitabine-efavirenz treatment on the growth of breast feeding infants Outhoff, Kim kayilpillay@gmail.com Brand, Sarel Feucht, Ute Dagmar Pillay, Kaylene UCTD Sustainable Development Goals (SDGs) Tenofovir disoproxil fumarate (TDF) Infant growth Breast feeding HIV-exposed uninfected (HEU) infants Macronutrient content Liquid chromatography-tandem mass spectrometry (LC MS/MS) Infant growth trajectories Antiretroviral (ARV) drug exposure Nutritional support Dissertation (MSc)--University of Pretoria, 2025. Background: In South Africa, nearly a quarter of women of reproductive age live with HIV, resulting in a growing population of infants exposed to HIV and antiretroviral (ARV) medications both in utero and postpartum. This study aimed to explore critical concerns regarding the impact of ARV medication, particularly tenofovir disoproxil fumarate (TDF), on the growth of infants breastfed by women living with HIV (WLWHIV). Methodology: This study used previously obtained breast milk samples and growth data from the UmbiBaby study carried out in the Tshwane District. Breast milk samples were collected from 26 WLWHIV receiving TDF treatment and from a control group of 65 mothers not living with HIV at 14 weeks postpartum. Breast milk samples were analysed using LC-MS/MS to detect the presence of tenofovir (TFV) and its metabolites. Quantification was not performed due to sensitivity limitations. Macronutrient contents were assessed using a Miris Human Milk Analyser (HMA). Infant growth parameters were extracted from the REDCap database and assessed using a retrospective cohort design, focussing on mean anthropometry z-scores based on WHO standards and comparing HIV-exposed and uninfected (HEU) and HIV-unexposed and uninfected (HUU) infants from 6 weeks to 24 months of age through longitudinal analysis. Results: The optimised LC-MS/MS method detected TFV within a calibration range of 50–200 ng/mL (R² = 0.9945). Methodological challenges included matrix effects and limited instrument sensitivity, which restricted the lower limit of detection to 50 ng/mL for TFV. However, TFV-DP quantification was hindered by chemical instability and in-source fragmentation. The results confirmed that TFV concentrations in breast milk were well below paediatric therapeutic doses, supporting the safety of breastfeeding for WLWHIV on TDF therapy. Macronutrient analysis revealed breastfeeding rates were significantly lower among HEU infants from 6 months onward (p-values ranging from 0.0250 to 0.0065). Significantly higher protein content was detected in the breast milk of WLWHIV compared to controls at 6 weeks (p = 0.0074) and 18 months (p < 0.0001). Fat and energy content were significantly higher in the WLWHIV group at 12 months (fat: p = 0.0088; energy: p = 0.0015) and 18 months (fat: p = 0.0163; energy: p = 0.0099). Carbohydrate content remained stable between groups, with significant differences at 12 months (p = 0.0021) and 18 months (p = 0.0471). Infant growth analysis showed that HEU infants had lower weight-for-age z-scores at 6 weeks (p = 0.0223) and 14 weeks (p = 0.0294) compared to HUU infants. Length-for-age z-scores were significantly lower in HEU infants at 6 weeks (p = 0.0009), 14 weeks (p = 0.0006), 9 months (p = 0.0027), and 24 months (p = 0.0492). Weight-for-length (WFL) and body mass index-for-age (BMIZ) z-scores showed no significant differences between HEU and HIV-unexposed uninfected (HUU) infants throughout the study period. Conclusion: Although TFV and its metabolites were not quantified, the consistent macronutrient content of breast milk and mixed infant growth outcomes suggest that ARV exposure via breastfeeding may be limited. This warrants further investigation with more sensitive methods. The observed disparities in growth outcomes for HEU infants emphasize the need for early nutritional support and interventions. This study highlights the complex interplay between HIV exposure, TDF and breast feeding, macronutrient content, and infant growth. The findings will contribute to optimising ARV strategies for pregnant and lactating WLWHIV, ultimately fostering infant health. Keywords: Tenofovir Disoproxil Fumarate, Infant Growth, Breast feeding, HIV-Exposed Uninfected (HEU) Infants, Macronutrient Content, Antiretroviral Therapy, LC-MS/MS, Infant Growth Trajectories, ARV Drug Exposure, Nutritional Support National Research Foundation (NRF) Thuthuka Grant Pharmacology MSc (Pharmacology) Unrestricted Faculty of Health Sciences SDG-03: Good health and well-being 2025-02-28T12:44:20Z 2025-02-28T12:44:20Z 2025-05-02 10-12-2024 Dissertation * A2025 http://hdl.handle.net/2263/101286 DOI: https://doi.org/10.25403/UPresearchdata.28511996.v1 10.25403/UPresearchdata.28511996 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria
spellingShingle UCTD
Sustainable Development Goals (SDGs)
Tenofovir disoproxil fumarate (TDF)
Infant growth
Breast feeding
HIV-exposed uninfected (HEU) infants
Macronutrient content
Liquid chromatography-tandem mass spectrometry (LC MS/MS)
Infant growth trajectories
Antiretroviral (ARV) drug exposure
Nutritional support
The effects of maternal tenofovir disoproxil fumarate-emtricitabine-efavirenz treatment on the growth of breast feeding infants
title The effects of maternal tenofovir disoproxil fumarate-emtricitabine-efavirenz treatment on the growth of breast feeding infants
title_full The effects of maternal tenofovir disoproxil fumarate-emtricitabine-efavirenz treatment on the growth of breast feeding infants
title_fullStr The effects of maternal tenofovir disoproxil fumarate-emtricitabine-efavirenz treatment on the growth of breast feeding infants
title_full_unstemmed The effects of maternal tenofovir disoproxil fumarate-emtricitabine-efavirenz treatment on the growth of breast feeding infants
title_short The effects of maternal tenofovir disoproxil fumarate-emtricitabine-efavirenz treatment on the growth of breast feeding infants
title_sort effects of maternal tenofovir disoproxil fumarate emtricitabine efavirenz treatment on the growth of breast feeding infants
topic UCTD
Sustainable Development Goals (SDGs)
Tenofovir disoproxil fumarate (TDF)
Infant growth
Breast feeding
HIV-exposed uninfected (HEU) infants
Macronutrient content
Liquid chromatography-tandem mass spectrometry (LC MS/MS)
Infant growth trajectories
Antiretroviral (ARV) drug exposure
Nutritional support
url http://hdl.handle.net/2263/101286