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 recently 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. We will compare micronucleus frequencies in cord blood reticulocytes of ZDV-exposed babies to micronucleus frequencies in a control group of non-exposed babies born to healthy HIV-negative women. To acquire additional data to more fully explore the potential for ZDV-induced chromosomal damage in neonates, we propose to assess frequencies of micronucleated reticulocytes in HIV-infected pregnant women prior to or during labor, and in their infants 1 day, 6 weeks and 6 months after treatment. Hospital staff at UNC Hospitals and Duke University Medical Center will recruit HIV-infected pregnant women to participate in this study. We anticipate that we will need at least one year to accrue 5 HIV-infected women and their babies from each institution into the study. Each institution will also provide cord bloods from 5 non-HIV infected, non-exposed controls. MNE from each of these samples will be determined using newly developed flow cytometric methods.
| 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 |
