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HIV Therapy for Pregnant Mothers
  BOSTON (Susman, UPI Science News, Feb 15, 2002) -- Drugs that prevent the transmission of the AIDS virus from infected mothers to their newborns appear to cause mutations in the babies' DNA at twice the rate seen in normal children, researchers said Friday.
"We really don't know what this means as far as future problems, such as the risk of cancer," said Vernon Walker, research scientist at the Lovelace Respiratory Research Institute, Albuquerque, N.M.
"However, it does indicate that warnings about future health problems that were promulgated by the Food and Drug Administration about use of these drugs in pregnant women were justified," he told United Press International.
So far, Walker said during a news briefing Friday at the annual meeting of the American Association for the Advancement of Science, there are no cases in which cancer related to use of the drugs has been reported in the children.
Walker said all children are born with a few DNA mutations. In his study, the average number of mutations among 68 children unexposed to the antiretroviral drugs used to treat patients with the virus was 1.3 per million cells.
However among those 71 babies whose mothers took zidovudine or AZT and/or lamuvidine or 3TC to prevent transmission of the human immunodeficiency virus, there were an average of 2.6 mutations per million cells -- twice as many.
In another way of measuring the effect of the drugs on the newborns, Walker said about 3 percent of the unexposed children had mutations that indicate an abnormal protein was created by the DNA damage. Among children born to mothers who took AZT or both drugs, these types of mutations occurred in 9 percent to 14 percent of the babies.
"Both those figures are significantly greater than the unexposed children," Walker said.
AZT and 3TC are drugs in the class of nucleoside reverse transcriptase inhibitors. The drugs integrate into the DNA of the virus, crippling its ability to reproduce. However, the drugs also incorporate themselves into the DNA of normal cells and this change may be transmitted to offspring.
"DNA damage accumulates through a person's lifetime," Walker said. "These babies whose mothers received AZT and 3TC have the accumulated DNA mutations one would expect to see in teenagers."
He noted because treatment of pregnant women infected with HIV, which causes AIDS, prevents transmission of the virus, the benefit appears to far outweigh the possibility of a risk of serious disease, such as cancer, down the road. Children who took AZT in early studies, done to show it could prevent virus transmission, now are about around 7 years old.
"But," Walker said, "these studies show that the transmission of these mutations are more than just theoretical."
Stephanie Bird, special assistant to the provost at Massachusetts Institute of Technology in Cambridge and a health ethicist, said the findings indicate there is an ethical problem in treating mothers with the drugs.
She said damage to DNA not only can result in cancer, but might also cause heart and other developmental abnormalities.
Bird suggested if the it turns out consequences later on are severe, parents would have to weigh the possibility of not taking the drugs and then treating children who are born infected with HIV.
Walker noted about 25 percent of babies born to untreated mothers have HIV at birth.
With effective treatment, that number is virtually nil.
"Nobody has focused at all on what these drugs may be doing," said Rochelle Diamond, chair of the National Organization of Gay and Lesbian Scientists and a member of the professional staff at California Institute of Technology, Pasadena. "Would-be parents need to know that there is a minimal risk in taking these drugs."
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