Antiretroviral therapies with dideoxynucleosides, such as ZDV, have not been adequately examined for potential reproductive or long term mutagenic effects in humans. Such investigation is warranted given that genetic damage in humans and genetic plus reproductive effects in animals have been reported following ZDV exposure, and the data obtained would be of help to individuals and their physicians in making more informed risk/benefit decisions about the use of these therapies. Cytogenetic effects in blood lymphocytes, and both fertility and cytogenetic parameters in sperm, were evaluated (repeated measures design) for individuals preparing to start dideoxynucleoside therapy and one to two times during dideoxynucleoside therapy and, for the occupationally exposed group, post-dideoxynucleoside therapy. During the past year, the Clinical Centers completed enrollment and sampling of all study subjects. A total of 30 subjects were enrolled. Four (4 ) were individuals occupationally exposed to HIV who elected to undergo prophylactic antiretroviral drug therapy. Two(2) were females. Of the two males who were occupationally exposed, one elected not to take the prophylactic drug treatments and thus became our one negative control. The remaining 26 males who were enrolled were all HIV positive. Eighty- two (82) blood samples from these 30 individuals were processed for lymphocyte cytogenetic analysis. CASA and standard semen analyses were performed on 82 samples from 25 male patients, with slides for 75 of these samples evaluated for abnormal morphology. Twenty-three (23) sperm samples from 9 HIV positive men were evaluated for aneuploidy by a novel fluorescence in situ hybridization (FISH) analysis of sperm; 11 samples from 7 of these men were also evaluated for chromosome breakage using another novel sperm-FISH assay. Preliminary statistical analyses indicate there were no adverse treatment related effects on any of the endpoints evaluated. Several semen parameters, however, appeared to improve with increased treatment time. - reproductive failure, birth defects, aneuploidy, infertility, mutations, chromosome aberrations - Human Subjects
| Robbins, W A; Witt, K L; Haseman, J K et al. (2001) Antiretroviral therapy effects on genetic and morphologic end points in lymphocytes and sperm of men with human immunodeficiency virus infection. J Infect Dis 184:127-35 |
| Marchetti, F; Bishop, J B; Lowe, X et al. (2001) Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse. Proc Natl Acad Sci U S A 98:3952-7 |
| Schmid, T E; Lowe, X; Marchetti, F et al. (2001) Evaluation of inter-scorer and inter-laboratory reliability of the mouse epididymal sperm aneuploidy (m-ESA) assay. Mutagenesis 16:189-95 |
