Hendricks, Candice LaverneEllero, Andrea AntonioMellet, JuanitaStivaktas, VoulaPepper, Michael Sean2025-09-172025-09-172025-04Hendricks, C.L., Ellero, A., Mellet, J. et al. 2025, 'Antiretroviral-induced toxicity in umbilical cord blood-derived haematopoietic stem/progenitor cells', Journal of Cellular and Molecular Medicine, vol. 29, no. 8, art. e70557, pp. 1-13, doi : 10.1111/jcmm.70557.1582-1838 (print)1582-4934 (online)10.1111/jcmm.70557http://hdl.handle.net/2263/104354DATA AVAILABILITY STATEMENT : For original flow cytometry data files, please contact michael.pepper@up.ac.za. SUPPORTING INFORMATION FIGURE S1. Effect of LDH release upon acute drug exposures. FIGURE S2. Lin-CD34+ Immunophenotypic sub-populations on D7. FIGURE S3. Identification of the significantly different Lin-CD34+ MC phenotypes after. FIGURE S4. Colony forming unit immunophenotypic sub-populations. FIGURE S5. Differences in immunophenotypic sub-populations identified between TLD.Improvements in administration and efficacy of antiretroviral therapy (ART) have reduced rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) to < 2%. However, in utero exposure to antiretrovirals (ARVs) leads to abnormalities in HIV-exposed uninfected (HEU) infants. We determined the effect of five ARVs on human umbilical cord blood (UCB)-derived haematopoietic stem/progenitor cells (HSPC) with the aim of exploring a potential causal relationship with haematological abnormalities. Efavirenz (EFV) was cytotoxic to HSPCs alone and in combination with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Dolutegravir (DTG) had a biphasic effect on HSPC expansion. Immunophenotypic analysis showed increased erythroid and granulocyte precursors after 7-day culture with these drugs. Finally, using colony forming unit (CFU) assays, we observed impairment in the formation of CFU-GEMM and CFU/Burst forming unit (BFU) erythroid (E) in the presence of DTG, lamivudine (3TC) and TDF, both visually and immunophenotypically. We conclude that multiple potential HSPC toxicities exist with ARVs commonly used in pregnancy, prompting the need for further research to confirm the safety of these drugs in this vulnerable group.en© 2025 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License.Antiretroviral therapy (ART)Mother-to-child transmission (MTCT)Human immunodeficiency virus (HIV)Antiretrovirals (ARVs)HIV-exposed uninfected (HEU)InfantsUmbilical cord blood (UCB)Haematopoietic stem/progenitor cells (HSPC)Efavirenz (EFV)Tenofovir disoproxil fumarate (TDF)Dolutegravir (DTG)ARV toxicityColony forming unitsImmunophenotypeIn utero ARV exposureUmbilical cord blood haematopoietic stem cellsArticle