title: Elevated frequencies of micronucleated erythrocytes in infants exposed to zidovudine in utero and postpartum to prevent mother-to-child transmission of HIV.
abstract: Zidovudine-based antiretroviral therapies (ARTs) for treatment of HIV-infected pregnant women have markedly reduced mother-to-child transmission of the human immunodeficiency virus (HIV-1) from approximately 25% to <1%. However, zidovudine (ZDV; AZT), a nucleoside analogue, induces chromosomal damage, gene mutations, and cancer in animals following direct or transplacental exposure. To determine if chromosomal damage is induced by ZDV in infants exposed transplacentally, we evaluated micronucleated reticulocyte frequencies (%MN-RET) in 16 HIV-infected ART-treated mother-infant pairs. Thirteen women received prenatal ART containing ZDV; three received ART without ZDV. All infants received ZDV for 6 weeks postpartum. 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 collected immediately after delivery. Ten cord blood samples (controls) were obtained from infants of HIV-uninfected women who did not receive ART. %MN-RET was measured using a single laser 3-color flow cytometric system. Tenfold increases in %MN-RET were seen in women and infants who received ZDV-containing ART prenatally; no increases were detected in three women and infants who received prenatal ART without ZDV. Specifically, mean %MN-RET in cord blood of ZDV-exposed infants was 1.67 +/- 0.34 compared with 0.16 +/- 0.06 in non-ZDV ART-exposed infants (P = 0.006) and 0.12 +/- 0.02 in control cord bloods (P < 0.0001). %MN-RET in ZDV-exposed newborns decreased over the first 6 months of life to levels comparable to cord blood controls. These results demonstrate that transplacentalZDV exposure is genotoxic in humans. Long-term monitoring of HIV-uninfected ZDV-exposed infants is recommended to ensure their continued health.
authors.affiliation: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Kristine L
authors.initials: KL
authors.lastname: Witt
authors.forename: Coleen K
authors.initials: CK
authors.lastname: Cunningham
authors.forename: Kristine B
authors.initials: KB
authors.lastname: Patterson
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Dertinger
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Livingston
authors.forename: Jack B
authors.initials: JB
authors.lastname: Bishop
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D008431:Maternal-Fetal Exchange; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D009153:Mutagens / Q000009:adverse effects*; D049590:Postpartum Period; D011247:Pregnancy; D012156:Reticulocytes / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D015215:Zidovudine / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D009153:Mutagens; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine