Brief Report: Breast Milk Transfer and Infant Exposures to Dolutegravir, Tenofovir, and Tenofovir Alafenamide: Results From IMPAACT 2010/VESTED
Year: 2025
Type: article
Abstract: BACKGROUND: Limited information is available on breast milk transfer and subsequent infant systemic exposure to dolutegravir (DTG), tenofovir alafenamide (TAF), and tenofovir (TFV). We evaluated concentrations of DTG, TAF, and TFV in maternal and infant plasma and breast milk from participants of International Maternal Pediatric Adolescent AIDS Clinical Trials 2010, a clinical trial that enrolled women initiating either a DTG-containing or an efavirenz-containing antiretroviral treatment regimen during pregnancy. METHODS: Time-matched postpartum maternal and infant samples were collected at 6 weeks postpartum. Validated assays quantitated concentrations of DTG, TAF, and TFV. Relative infant dose was estimated using an average milk intake of 150 mL/kg/d and observed breast milk concentrations. RESULTS: Data were available from 192 postpartum lactating women and their breastfed infants. Median maternal plasma concentrations of DTG, TAF, and TFV were 2810, 0.0, and 96 ng/mL, respectively. For DTG, median [interquartile range (IQR)] concentrations in breast milk and infant plasma were 91 ng/mL (67-123) and 69 ng/mL (41-95), respectively. TAF was below the quantitative limit (BQL) in nearly all breast milk and infant plasma samples. For TFV, median (IQR) concentrations in breast milk were 8 ng/mL (6-12), and nearly all infant plasma samples were BQL. The median RIDs of DTG, TAF, and TFV from breastfeeding were 1.9%, 0.00%, and 0.03%, respectively. CONCLUSIONS: Breast milk transfer of DTG, TAF, and TFV is low and results in minimal systemic exposure in breastfed infants. The clinical relevance of infant exposure to low concentrations of these antiretrovirals-particularly DTG-is unknown but should be considered in the context of the risk of drug resistance in infants who acquire HIV.
Authors: Tk Nguyen, Jung-Woo Chae, Lauren Ziemba, Anne Coletti, Kevin Knowles, Benjamin Johnston, Patrick Jean-Philippe, Tsungai Mhembere, Tariro Chawana, Deo Wabwire, Violet Korutaro, Sikhulile Moyo, Patricia Mandima, Siphokazi Sibisi, Avy Violari, Sherika Hanley, Blandina Mmbaga, Gaerolwe Masheto, Ponego Ponatshego, Gerhard Theron, Shilpa N. Naik, Roger Shapiro, Shahin Lockman, Lameck Chinula, Jeremiah D. Momper, for the IMPAACT 2010/VESTED Protocol Team
Institutions: University of California San Diego, Harvard University, Frontier Science & Technology Research Foundation, Inc., National Institutes of Health, University of Zimbabwe, Makerere University, Baylor College of Medicine Children’s Foundation, University of the Witwatersrand, University of KwaZulu-Natal, Kilimanjaro Christian Medical Centre, Stellenbosch University, Brigham and Women's Hospital, University of North Carolina at Chapel Hill, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Brigham and Women's Hospital, Purdue University, School of Medicine, Boston University, Seattle Children's Research Institute, Children’s Hospital of Wisconsin Research Institute, International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: SDMC - IMPAACT Leadership Group, International Maternal, Adolescent and Pediatric Therapeutics Clinical Trials Network, Botswana-Harvard T.H. Chan School of Public Health AIDS Initiative Partnership CTU, Stellenbosch University Clinical Trials Unit, The Johns Hopkins University - Uganda Clinical Trials Unit, KwaZulu-Natal Clinical Trials Unit, PHRU-Setshaba Clinical Trials Unit, IMPAACT Leadership Group
OpenAlex ID: W4415960631
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