July 1, 1998
The new guidelines for antiviral therapy suggest that we should consider the best antiviral therapy for a pregnant woman based on the best therapy for her, initially ignoring her pregnancy, and then considering how that influences risks and benefits. The woman should understand the risks, benefits and the unknowns and actively participate in the choices. This means triple therapy for many pregnant women with significant HIV disease. This is clearly the only right approach in my mind, but some have considered it controversial. We must remember though, that we do not have long term safety or efficacy information for "HAART" in pregnancy. The abstract below was extremely important, and it matches what many of us have seen in smaller series.
Session 459/12151: Control of maternal HIV-1 disease during pregnancy
Karen Beckerman presented the experience at the Bay Area Perinatal AIDS Center at San Francisco General. They have a multidisciplinary comprehensive program for HIV-infected pregnant women. Since 1996, an increasing proportion of the mothers chose double or triple combination therapy. In the most recent group, more than 80% have chosen protease containing therapy. Most mothers had undetectable viral loads at delivery with this approach. Of the last 61 pregnant women, 60 have had uninfected babies. The mother who transmitted was not on medication during the third trimester. Side effects were those typically encountered with the drugs, and no unexpected adverse outcomes have been seen in the babies. This is extremely good news. Although it is not a controlled study, it suggests that more potent therapies may drive the transmission rate from mother to child from the 8% seen with AZT monotherapy in ACTG 076 to closer to 1 or 2%, while providing women with the state of the art antiviral therapy. This may come from lowering cell associated virus and perhaps lowering virus in other compartments.
It is important to keep looking very hard at the safety of these drugs in pregnancy, although we should not deny them to women just because the studies are not in yet. However, there may be surprises. It is likely that all drugs are not equally safe. Efavirenz is the only one to clearly cause birth defects in monkeys, and women who are or want to become pregnant should choose other drugs. An observational study from the Geneva group raised some concerns
Poster Session 32453: Safety of combined therapies in pregnancy
The group reported on 37 consecutive pregnant women treated with triple combination therapy. Since they defined an adverse event as any abnormal lab value, it was not surprising that lab adverse events were common in mothers, but mostly consisted of abnormal liver function tests, abnormal bilirubin, and some anemia, all quite common in any group of patients on AZT, indinavir, or ritonavir. Two women had kidney stones on indinavir (CRIXIVAN). One woman had an ectopic pregnancy; she was taking hydroxyurea when she became pregnant. 30 babies have been delivered so far. 8 were anemic, a minor complication often seen in the first 6 weeks when the baby is on AZT. One third of the babies were born prematurely, although most apparently were not significantly premature. Two babies whose mothers were on indinavir had intracerebral hemorrhages. One was a premie, where this is a common complication but the other was born at term. One baby, also exposed to indinavir had biliary atresia, a rare birth defect. Their conclusion, and I suppose mine as well, was that the complications in the mother were what one would expect on treatment. Three unexpected events were seen in 30 children, but there is no way of knowing whether these were related to the drugs unless more cases appear and a comparison can be made with an HIV-infected group not on therapy. However, we clearly need to keep watching, and sharing the information as it becomes available. I have tended to recommend nelfinavir in pregnancy because of timing of meals, worry about kidney stones in mothers and not knowing if the elevated bilirubin in adults might mean some liver toxicity for a fetus, but it is mostly instinct until we have trials.