# Antiretroviral‐Induced Toxicity in Umbilical Cord Blood‐Derived Haematopoietic Stem/Progenitor Cells

## TL;DR

This study explores how antiretroviral drugs used during pregnancy may harm blood stem cells in infants, potentially causing blood-related issues.

## Contribution

The study identifies specific antiretroviral drugs that are toxic to umbilical cord blood-derived hematopoietic stem/progenitor cells.

## Key findings

- Efavirenz is cytotoxic to hematopoietic stem/progenitor cells alone and in combination with other drugs.
- Dolutegravir shows a biphasic effect on stem cell expansion and impairs colony formation.
- ARVs impair the formation of erythroid and granulocyte precursors in stem cell cultures.

## Abstract

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.