HIV-infected pregnant women are administered nucleoside-analogue antiretrovirals to reduce maternal-infant viral transmission. The current Public Heath Service protocol also recommends treating newborns for 6 additional weeks postpartum. The treatment is extremely effective in reducing the rate of infection in these infants, but the risk for drug-induced chromosomal damage in human neonates remains undefined, although there are sufficient data from studies with laboratory animals to consider this potential a valid concern. We have previously shown that mouse pups, exposed in utero, and postnatally via lactation and direct gavage to zidudovine (ZDV) exhibit extremely elevated frequencies of micronucleated erythrocytes (MNE) in their peripheral blood. We believe it is important to understand whether these effects of ZDV seen in mouse pups also occur in human infants exposed to ZDV and/or other AIDs drugs. To determine if chromosomal damage is induced by ZDV in humans exposed in utero, we performed a case-control study evaluating micronucleated reticulocytes (MN-RET) in 16 HIV-infected ART-treated mother-infant pairs and 10 cord blood samples from infants born to HIV-uninfected women. Venous blood was obtained from women at delivery, and from infants at 1-3 days, 4-6 weeks, and 4-6 months of life; cord blood was also collected immediately after delivery. MN-RET frequencies were measured using a single laser 3-color flow cytometric system. The results of this study, which demonstrate that transplacental ZDV exposure is genotoxic to human infants exposed to ZDV in utero, have been submitted for publication. We recommend long-term monitoring of HIV-uninfected ZDV-exposed infants to ensure their continued health.
| Witt, Kristine L; Tice, Raymond R; Wolfe, Gary W et al. (2004) Genetic damage detected in CD-1 mouse pups exposed perinatally to 3'-azido-3'-deoxythymidine or dideoxyinosine via maternal dosing, nursing, and direct gavage: II. Effects of the individual agents compared to combination treatment. Environ Mol Mutagen 44:321-8 |
| Bishop, Jack B; Tani, Yoshiro; Witt, Kristine et al. (2004) Mitochondrial damage revealed by morphometric and semiquantitative analysis of mouse pup cardiomyocytes following in utero and postnatal exposure to zidovudine and lamivudine. Toxicol Sci 81:512-7 |
