Gay Men's Health Crisis: Treatment Issues, Volume 8 no. 2 - April, 1994
Dave Gilden

Many questions remain about the role of AZT therapy in pregnancy. The study is characterized by Rhoda Sperling, a physician at Mt. Sinai Hospital in New York and one of ACTG 076's principal investigators, as a "best shot" trial to prove the principal that AZT can reduce the transmission of HIV from mother to infant. The study did not examine AZT's mechanism of action in this situation or find ways of predicting in which women it would be effective. The study's applicability is limited despite fears that it will lead to mandatory HIV testing of pregnant women.

Trial participants were relatively healthy - all had CD4 counts of at least 200 and half had counts greater than 500. None had a particular medical reason to be on AZT during their pregnancy. All the women were receiving regular prenatal care at the participating hospitals.

The women received 500mg of AZT daily or a placebo. Treatment started sometime after the fourteenth week of pregnancy and was followed by a continuous infusion of AZT or placebo during labor. AZT or, again, placebo was also administered to the babies for six weeks following birth.

The drug may have reduced transmission by lowering HIV levels in mothers, in which case the question is when in pregnancy or labor it is most important. Most mother-to-child transmission seems to take place at the time of birth, but a significant amount of in utero transmission is also thought to occur.

AZT also may have functioned as a primary prophylaxis in the fetuses and newborn babies, preventing the infection of any of their cells. This would argue for administering AZT prior to birth as well as afterward.

There have been many concerns about AZT's potential for causing birth defects. Reducing the risk of congenital abnormalities was the reason researchers waited until after the fourteenth week of pregnancy to initiate therapy. As it was, birth defects were evenly balanced between participants on AZT and those on placebo. The only significant anomaly found so far was a minor hemoglobin decrease in the babies receiving AZT. Hemoglobin levels soon normalized when AZT administration ended six weeks after delivery. Researchers agree, though, that the long-term dangers AZT poses for infants is unknown. They plan to follow the children for as long as 21 years.

Previously, there has not been much reason to test pregnant women for HIV. ACTG 076 now raises the possibility that prenatal programs will require expectant mothers be tested so that the ones who are positive receive AZT. Such a policy could backfire by scaring away women who are most at risk, in which case they would receive no prenatal care at all.

Coming months will see considerable discussion among professional and activist groups about the guidelines for applying ACTG 076 to medical practice. Abrupt changes in policy seem premature: The results of ACTG 076 indicate that AZT only prevents HIV transmission in about one-sixth of the mothers and babies treated. The outcome for the rest is the same whether AZT is used or not.

The study did not include women with severely compromised immune systems. In addition, the impact of having AZT- resistant virus has not yet been examined. So far, there is no definitive way to evaluate the risks versus benefits of AZT for an individual mother.

Dr. Sperling says that further analysis of HIV levels and immune function in the study's participants will take place this year. That analysis could provide more information about when AZT is effective in preventing mother-to-child transmission and when it is not.

Alternatives to AZT are under development, too. At present, there are ongoing trials of the drug nevirapine and HIV immunoglobulin (passive transfers of anti-HIV antibodies extracted from healthy, HIV-positive people). Either of these probably has less toxic effects than AZT.

Dr. Sperling says, "The entire perinatal agenda needs to be reviewed, both ethically and scientifically This study is another piece of information that should be discussed with every pregnant woman."

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