BETHESDA, Md--A federal advisory committee has recommended continuing
the use of AZT (zidovudine) in HIV-infected pregnant women to prevent them
from passing the virus on to their newborns. The group also urged the US
Public Health Service to thoroughly reassess its guidelines for the use
of AZT in pregnant women.
The National Institutes of Health convened the panel to consider the
conflicting findings of two studies in pregnant mice, one of which found
a significant increased risk of cancer in the offspring of animals treated
In that study, by researchers at the National Cancer Institute, female
mice were given very high doses of the drug during the last trimester (days
12 to 18 of gestation) and their pups followed for 12 months. These offspring
showed a several-fold increase in the incidence of liver and lung tumors,
and unusual reproductive-organ tumors in 17% of the females.
However, a second study, by researchers at Glaxo Wellcome, Inc., the
drug's manufacturer, found no increase in tumor incidence. This study used
several regimens of AZT at doses intended to achieve blood levels of the
drug about three times higher than the therapeutic dose in humans. These
daily doses ranged from one-twelfth to one-fiftieth the daily dose used
in the NCI study.
The NIH panel said that with the significant differences in design,
it was not surprising that the two studies reached such different conclusions.
The panel noted that studies continue to indicate that AZT significantly
lowers the infection rate of infants born to HIV-positive women: The AIDS
Clinical Trials Group protocol 076 has shown a reduction in the rate of
maternal-fetal transmission from 22.6% to 7.6%; a study of 500 women in
New York, Boston, Chicago, Houston, and Puerto Rico found the drug lowered
infections from 19% to 8%; and in a North Carolina study, the transmission
rate fell from 21% to 10%.
Moreover, three years of follow-up have yet to find a single tumor in
some 1,000 children whose mothers took AZT while pregnant.
The panel unanimously concluded that AZT's known benefits in blocking
perinatal HIV transmission far outweigh "the hypothetical concerns
of transplacental carcinogenesis raised by the NCI mouse study."
Nonetheless, the group emphasized that physicians must thoroughly discuss
the theoretical risk raised by the study with pregnant HIV-positive women
in the course of counseling them on the risks and benefits of AZT, both
in clinical trials and as a preventive therapy.
The panel also emphasized the need for careful, long-term study of children
exposed in utero to antiretroviral therapy, and urged NCI researchers to
complete a full, two-year follow-up of the mice remaining in their experiment.
Finally, the advisory committee noted that antiretroviral therapy has
changed substantially since the Public Health Service recommended the use
of AZT in pregnant women. Therefore, it recommended that the agency reconvene
its task force to carry out a thorough reassessment of the guidelines.