{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:58:17Z","timestamp":1792979897035,"version":"4.5.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Freiburg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Adherence to antiretroviral therapy (ART) and maintaining an undetectable maternal HIV viral load effectively prevent intrauterine and perinatal HIV transmission 1, 2. However, concerns remain regarding the safety of breastfeeding in infants exposed to maternal ART. This retrospective study analyzed eight breastfed HIV-exposed uninfected (HEU) infants who were followed from January 2015 to July 2022. Maternal ART regimens included abacavir\/lamivudine (n\u2009=\u20092), tenofovir alafenamide\/emtricitabine (n\u2009=\u20091) or tenofovirdisoproxil\/emtricitabine (n\u2009=\u20095) in combinations with rilpivirine (n\u2009=\u20093) (RPV), dolutegravir (n\u2009=\u20092) (DTG), raltegravir (n\u2009=\u20091), darunavir\/ritonavir (n\u2009=\u20091), or nevirapine (n\u2009=\u20091). Infants and mothers underwent sequential HIV-PCR testing, complete blood count, and ART drug monitoring in breast milk, infant serum, and maternal serum when available. The relative infant dose (RID) was calculated to assess drug exposure. Hematological parameters were compared with those of 62 HEU formula-fed infants from the same institution. No HIV transmission occurred. ART serum levels in breastfed infants varied significantly, with RPV and DTG levels above the adult target range in two cases. Notably, one infant had RPV levels exceeding the target RID by 633%, leading to cessation of breastfeeding. At four months, mean absolute neutrophil counts were lower in breastfed infants (1,130\/\u00b5l) compared to formula-fed infants (2,000\/\u00b5l), with the lowest individual absolute neutrophil counts in the formula-fed group. Despite ART levels above the adult target range in 3 infants, there was no consistent pattern between neutropenia and elevated ART levels. Our findings highlight the substantial variability in infant ART exposure during breastfeeding. Given this variability and the potential for drug accumulation in individual cases, maternal therapeutic drug monitoring should be considered to identify elevated levels early on. In such situations, infant monitoring tailored to the individual may also be warranted.<\/jats:p>","DOI":"10.1038\/s41598-025-20259-4","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T11:16:04Z","timestamp":1758194164000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Breastfeeding on ART and a closer look at drug transfer to HIV-exposed uninfected infants"],"prefix":"10.1038","volume":"15","author":[{"given":"Benedikt D.","family":"Spielberger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Zink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan C.","family":"Rohr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Usadel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartwig","family":"Klinker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Freudenhammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Elling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegbert","family":"Rieg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Henneke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hufnagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias C.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"issue":"3","key":"20259_CR1","doi-asserted-by":"publisher","first-page":"e590","DOI":"10.1093\/cid\/ciac703","volume":"76","author":"J Sibiude","year":"2023","unstructured":"Sibiude, J. et al. Update of Perinatal Human Immunodeficiency Virus Type 1 Transmission in France: Zero Transmission for 5482 Mothers on Continuous Antiretroviral Therapy From Conception and With Undetectable Viral Load at Delivery. Clin. Infect. Dis. 76(3), e590\u2013e598 (2023).","journal-title":"Clin. Infect. Dis."},{"issue":"12","key":"20259_CR2","doi-asserted-by":"publisher","first-page":"3436","DOI":"10.1093\/jac\/dkac337","volume":"77","author":"K Aebi-Popp","year":"2022","unstructured":"Aebi-Popp, K. et al. Transfer of antiretroviral drugs into breastmilk: a prospective study from the Swiss Mother and Child HIV Cohort Study. J Antimicrob Chemother 77(12), 3436\u20133442 (2022).","journal-title":"J Antimicrob Chemother"},{"issue":"17","key":"20259_CR3","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1097\/QAD.0000000000001259","volume":"30","author":"R Kobbe","year":"2016","unstructured":"Kobbe, R. et al. Dolutegravir in breast milk and maternal and infant plasma during breastfeeding. AIDS 30(17), 2731\u20132733 (2016).","journal-title":"AIDS"},{"issue":"2","key":"20259_CR4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1089\/apc.2020.0223","volume":"35","author":"L Haberl","year":"2021","unstructured":"Haberl, L. et al. Not Recommended, But Done: Breastfeeding with HIV in Germany. AIDS Patient Care STDS 35(2), 33\u201338 (2021).","journal-title":"AIDS Patient Care STDS"},{"issue":"4","key":"20259_CR5","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1097\/QAI.0000000000001612","volume":"77","author":"PM Flynn","year":"2018","unstructured":"Flynn, P. M. et al. Prevention of HIV-1 Transmission Through Breastfeeding: Efficacy and Safety of Maternal Antiretroviral Therapy Versus Infant Nevirapine Prophylaxis for Duration of Breastfeeding in HIV-1-Infected Women With High CD4 Cell Count (IMPAACT PROMISE): A Randomized, Open-Label, Clinical Trial. J Acquir Immune Defic Syndr 77(4), 383\u2013392 (2018).","journal-title":"J Acquir Immune Defic Syndr"},{"key":"20259_CR6","unstructured":"Behrens, G. Deutsch-\u00d6sterreichische Leitlinie zur HIV-Therapie in der Schwangerschaft und bei HIVexponierten Neugeborenen. Available from: URL: https:\/\/register.awmf.org\/assets\/guidelines\/055-002l_S2k_HIV-Therapie-Schwangerschaft-und-HIV-exponierten_Neugeborenen_2020-10-verlaengert.pdf"},{"issue":"3","key":"20259_CR7","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1111\/hiv.13583","volume":"25","author":"A Keane","year":"2024","unstructured":"Keane, A. et al. Guidelines and practice of breastfeeding in women living with HIV-Results from the European INSURE survey. HIV Med 25(3), 391\u2013397 (2024).","journal-title":"HIV Med"},{"issue":"7","key":"20259_CR8","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1093\/jac\/dkv080","volume":"70","author":"CJ Waitt","year":"2015","unstructured":"Waitt, C. J., Garner, P., Bonnett, L. J., Khoo, S. H. & Else, L. J. Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies. J Antimicrob Chemother 70(7), 1928\u20131941 (2015).","journal-title":"J Antimicrob Chemother"},{"issue":"2","key":"20259_CR9","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s00431-022-04710-6","volume":"182","author":"\u00c1 Manzanares","year":"2023","unstructured":"Manzanares, \u00c1. et al. Increased risk of group B streptococcal sepsis and meningitis in HIV-exposed uninfected infants in a high-income country. Eur J Pediatr 182(2), 575\u2013579 (2023).","journal-title":"Eur J Pediatr"},{"issue":"1","key":"20259_CR10","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/cei.12251","volume":"176","author":"L Afran","year":"2014","unstructured":"Afran, L. et al. HIV-exposed uninfected children: a growing population with a vulnerable immune system?. Clin Exp Immunol 176(1), 11\u201322 (2014).","journal-title":"Clin Exp Immunol"},{"key":"20259_CR11","unstructured":"EACS Guidelines. Available from: URL: (2023). https:\/\/www.eacsociety.org\/media\/guidelines-12.0.pdf"},{"issue":"6","key":"20259_CR12","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.jpha.2016.05.008","volume":"6","author":"N Charbe","year":"2016","unstructured":"Charbe, N. et al. Development of an HPLC-UV assay method for the simultaneous quantification of nine antiretroviral agents in the plasma of HIV-infected patients. J Pharm Anal. 6(6), 396\u2013403 (2016).","journal-title":"J Pharm Anal."},{"issue":"2","key":"20259_CR13","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.therap.2023.01.008","volume":"78","author":"E Cardoso","year":"2023","unstructured":"Cardoso, E. et al. Maternal drugs and breastfeeding: Risk assessment from pharmacokinetics to safety evidence - A contribution from the ConcePTION project. Therapie 78(2), 149\u2013156 (2023).","journal-title":"Therapie"},{"issue":"10","key":"20259_CR14","doi-asserted-by":"publisher","first-page":"4311","DOI":"10.1111\/bcp.14538","volume":"88","author":"RHJ Verstegen","year":"2022","unstructured":"Verstegen, R. H. J., Anderson, P. O. & Ito, S. Infant drug exposure via breast milk. Br J Clin Pharmacol 88(10), 4311\u20134327. https:\/\/doi.org\/10.1111\/bcp.14538 (2022).","journal-title":"Br J Clin Pharmacol"},{"issue":"7","key":"20259_CR15","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1097\/INF.0000000000002357","volume":"38","author":"TTT Nguyen","year":"2019","unstructured":"Nguyen, T. T. T. et al. Reducing hematologic toxicity with short course postexposure prophylaxis with Zidovudine for HIV-1 exposed infants with low transmission risk. Pediatr. Infect. Dis. J. 38 (7), 727\u2013730 (2019).","journal-title":"Pediatr. Infect. Dis. J."},{"issue":"1","key":"20259_CR16","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/cpt.377","volume":"100","author":"PO Anderson","year":"2016","unstructured":"Anderson, P. O. & Sauberan, J. B. Modeling drug passage into human milk. Clin Pharmacol Ther. 100(1), 42\u201352 (2016).","journal-title":"Clin Pharmacol Ther."},{"issue":"445","key":"20259_CR17","first-page":"1","volume":"132","author":"ER Larsen","year":"2015","unstructured":"Larsen, E. R. et al. Use of psychotropic drugs during pregnancy and breast-feeding. Psychiatr Scand Suppl 132(445), 1\u201328 (2015).","journal-title":"Psychiatr Scand Suppl"},{"issue":"4","key":"20259_CR18","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1097\/QAI.0000000000003075","volume":"91","author":"F Weiss","year":"2022","unstructured":"Weiss, F. et al. Brief report: HIV-Positive and breastfeeding in High-Income settings: 5-Year experience from a perinatal center in Germany. J. Acquir. Immune Defic. Syndr. 91 (4), 364\u2013367 (2022).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"issue":"10","key":"20259_CR19","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1093\/cid\/ciad235","volume":"77","author":"J Levison","year":"2023","unstructured":"Levison, J. et al. Breastfeeding Among People With Human Immunodeficiency Virus in North America: A Multisite Study. Clin Infect Dis 77(10), 1416\u20131422 (2023).","journal-title":"Clin Infect Dis"},{"issue":"7","key":"20259_CR20","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1097\/01.aids.0000166093.16446.c9","volume":"19","author":"PJ Iliff","year":"2005","unstructured":"Iliff, P. J. et al. Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival. AIDS 19(7), 699\u2013708 (2005).","journal-title":"AIDS"},{"issue":"9567","key":"20259_CR21","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/S0140-6736(07)60283-9","volume":"369","author":"HM Coovadia","year":"2007","unstructured":"Coovadia, H. M. et al. Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study. The Lancet 369(9567), 1107\u20131116 (2007).","journal-title":"The Lancet"},{"issue":"8","key":"20259_CR22","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1001\/jama.282.8.744","volume":"282","author":"PG Miotti","year":"1999","unstructured":"Miotti, P. G. et al. HIV transmission through breastfeeding: a study in Malawi. JAMA 282 (8), 744\u2013749 (1999).","journal-title":"JAMA"},{"issue":"2","key":"20259_CR23","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/toxsci\/66.2.185","volume":"66","author":"G Ginsberg","year":"2002","unstructured":"Ginsberg, G. et al. Evaluation of child\/adult pharmacokinetic differences from a database derived from the therapeutic drug literature. Toxicol Sci. 66(2), 185\u2013200 (2002).","journal-title":"Toxicol Sci."},{"issue":"14","key":"20259_CR24","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1097\/QAD.0000000000003043","volume":"35","author":"C Pressiat","year":"2021","unstructured":"Pressiat, C. et al. High nevirapine levels in breast milk and consequences in HIV-infected child when initiated on antiretroviral therapy. AIDS 35(14), 2409\u20132410 (2021).","journal-title":"AIDS"},{"issue":"4","key":"20259_CR25","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1097\/00002030-199903110-00006","volume":"13","author":"P Musoke","year":"1999","unstructured":"Musoke, P. et al. A phase I\/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006). AIDS 13(4), 479\u2013486 (1999).","journal-title":"AIDS"},{"issue":"6","key":"20259_CR26","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/S0149-2918(98)80105-7","volume":"20","author":"RB Pollard","year":"1998","unstructured":"Pollard, R. B., Robinson, P. & Dransfield, K. Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. Clin. Ther. 20 (6), 1071\u20131092 (1998).","journal-title":"Clin. Ther."},{"key":"20259_CR27","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.placenta.2020.07.009","volume":"100","author":"JF Robinson","year":"2020","unstructured":"Robinson, J. F., Hamilton, E. G., Lam, J., Chen, H. & Woodruff, T. J. Differences in cytochrome p450 enzyme expression and activity in fetal and adult tissues. Placenta 100, 35\u201344 (2020).","journal-title":"Placenta"},{"issue":"5","key":"20259_CR28","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1124\/dmd.110.037192","volume":"39","author":"SJ Miyagi","year":"2011","unstructured":"Miyagi, S. J. & Collier, A. C. The development of UDP-glucuronosyltransferases 1A1 and 1A6 in the pediatric liver. Drug Metab Dispos 39(5), 912\u2013919 (2011).","journal-title":"Drug Metab Dispos"},{"key":"20259_CR29","doi-asserted-by":"publisher","first-page":"S42","DOI":"10.1002\/jcph.1493","volume":"59","author":"J Bad\u00e9e","year":"2019","unstructured":"Bad\u00e9e, J. et al. Characterization of the Ontogeny of Hepatic UDP-Glucuronosyltransferase Enzymes Based on Glucuronidation Activity Measured in Human Liver Microsomes. J. Clin. Pharmacol. 59, S42\u2013S55 (2019).","journal-title":"J. Clin. Pharmacol."},{"issue":"5","key":"20259_CR30","doi-asserted-by":"publisher","first-page":"e1200","DOI":"10.1093\/cid\/ciaa1861","volume":"73","author":"L Dickinson","year":"2021","unstructured":"Dickinson, L. et al. Infant Exposure to Dolutegravir Through Placental and Breast Milk Transfer: A Population Pharmacokinetic Analysis of DolPHIN-1. Clin Infect Dis 73(5), e1200\u2013e1207 (2021).","journal-title":"Clin Infect Dis"},{"issue":"3","key":"20259_CR31","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1093\/cid\/civ317","volume":"61","author":"A Olagunju","year":"2015","unstructured":"Olagunju, A. et al. Breast milk pharmacokinetics of efavirenz and breastfed infants\u2019 exposure in genetically defined subgroups of mother-infant pairs: an observational study. Clin Infect Dis 61(3), 453\u2013463 (2015).","journal-title":"Clin Infect Dis"},{"issue":"8","key":"20259_CR32","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.3851\/IMP2314","volume":"17","author":"C Marzolini","year":"2012","unstructured":"Marzolini, C. & Gray, G. E. Maternal antiretroviral prophylaxis and breastfeeding. Antivir Ther 17(8), 1503\u20131506 (2012).","journal-title":"Antivir Ther"},{"issue":"2","key":"20259_CR33","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/nm1186","volume":"11","author":"JW Jonker","year":"2005","unstructured":"Jonker, J. W. et al. The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat Med 11(2), 127\u2013129 (2005).","journal-title":"Nat Med"},{"key":"20259_CR34","doi-asserted-by":"publisher","first-page":"107515","DOI":"10.1016\/j.intimp.2021.107515","volume":"95","author":"NM Nilavar","year":"2021","unstructured":"Nilavar, N. M. & Raghavan, S. C. HIV integrase inhibitors that inhibit strand transfer interact with RAG1 and hamper its activities. Int. Immunopharmacol. 95, 107515 (2021).","journal-title":"Int. Immunopharmacol."},{"key":"20259_CR35","doi-asserted-by":"publisher","first-page":"634386","DOI":"10.3389\/fimmu.2021.634386","volume":"12","author":"M Madzime","year":"2021","unstructured":"Madzime, M., Rossouw, T. M., Theron, A. J., Anderson, R. & Steel, H. C. Interactions of HIV and antiretroviral therapy with neutrophils and platelets. Front. Immunol. 12, 634386 (2021).","journal-title":"Front. Immunol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20259-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20259-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20259-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T11:16:07Z","timestamp":1758194167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-20259-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["20259"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-20259-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"assertion":[{"value":"4 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32612"}}