AIDSWEEKLY Plus; Monday, August 25, 2003
Staff Medical Writers

"Although children born to HIV-infected (HIV+) women receiving antiretroviral therapy during pregnancy show virtually no adverse clinical effects at birth, the antiretroviral nucleoside analog drugs are known to damage nuclear and mitochondrial DNA," researchers in the United States explained.

In a study conducted by M.C. Poirier and coauthors at the National Cancer Institute, "biomarkers of mitochondrial toxicity and genotoxicity" were examined "in a well-characterized sample set consisting of infants born to HIV-uninfected (HIV-) mothers (n=30), and HIV-infants (n=20) born to HIV-infected (HIV+) mothers who received either no antiretroviral therapy (n=10) or zidovudine (3'-azido-3'-deoxythymidine [AZT]) during pregnancy (n=10)."

"DNA from cord blood leukocytes and peripheral blood leukocytes taken at one and two years of age was examined for loss of mitochondrial DNA (mtDNA) and telomere integrity," they wrote in the Journal of Acquired Immune Deficiency Syndromes.

"Telomere length, a measure of nuclear DNA damage, was the same in all infants at birth and at age one year," test results indicated. "The quantity of mtDNA was assessed relative to nuclear DNA using a polymerase chain reaction-based chemiluminescence detection (PCR-CID) method that determined mitochondrial D Loop gene copies relative to nuclear 18S RNA gene copies by comparison with a standard curve."

"In infants of uninfected mothers (AZT-/HIV-) at the three time points, the ratios were 442 to 515, whereas in infants of untreated AZT-/HIV+ mothers the ratios were 261 to 297, and in infants of AZT-treated (AZT+/HIV+) mothers the ratios were 146 to 203," according to the report. "At all three time points, differences between the AZT-/HIV group and the two HIV+ groups were statistically significant (p<0.05), and differences between the AZT-/HIV+ and AZT+/HIV+ groups were also statistically significant (p<0.05), demonstrating that AZT exposure causes a persistent depletion of mtDNA."

"The study shows that children of HIV+ mothers are at risk for mitochondrial damage that is further increased in infants of mothers receiving AZT during pregnancy," the researchers concluded.

Poirier and colleagues published the results of their research in the Journal of Acquired Immune Deficiency Syndromes (Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected mothers. J Acquir Immune Defic Syndr. 2003 Jun 1;33(2):175-83.

For additional information, contact M.C. Poirier, NCI, Carcinogen-DNA Interactions Section, National Institutes of Health, Bldg. 37, Room 4032, 37 Convent Dr., MSC-4255, Bethesda, MD 20892, USA.

The publisher of the Journal of Acquired Immune Deficiency Syndromes can be contacted at: Lippincott Williams & Wilkins, 530 Walnut St., Philadelphia, PA 19106-3621, USA.

The information in this article comes under the major subject areas of Adverse Drug Effects, AIDS and HIV, DNA Research, Obstetric and Women's Health.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Poirier MC, Divi RL, Al-Harthi L, et al., "Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected mothers", J Acquir Immune Defic Syndr. 2003 Jun 1;33(2):175-83.

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