Bringing Up Baby
Last Summer, a small but alarming report from the World AIDS Conference in Geneva prompted federal researchers from the U.S. Pediatric AIDS Clinical Trials Group (PACTG) to put a temporary hold on enrolling pregnant women in early Phase I drug trials of protease inhibitors. The study, published in the December issue of AIDS by Swiss researcher Patrizio Lorenzi, found that women taking protease regimens had high rates of premature delivery and other adverse side effects.
Now a new French report has raised concerns over the safety of AZT and 3TC as well. Two HIV-negative babies who took the drugs died several month later of rare brain disease. Doctors are being cautioned about these risks. In the past, AZT monotherapy has been the standard treatment used to prevent perinatal transmission of HIV from a woman to her baby.
"The Geneva meeting raised concern about the risk-benefit ratio of using combination therapy during pregnancy," says Lynne Mofenson, a top pediatric researcher at the National Institutes of Health. In December, after a federal review of existing data on protease use and pregnancy, the PACTG team planned to reopen the drug trials in early 1999. But researchers concluded that further studies are needed to look at the effects of HIV infection on pregnant women, as well as the impact of combination HIV therapy. While the jury is still out on the benefit and possible toxicities of protease drugs, their decision cleared the way for studies that could provide much-needed information about optimum treatment for pregnant women. Up to now, only AZT and 3TC have been well evaluated in pregnant women and AZT studies have shown the drug appears safe for pregnant women. New data suggest it causes no significant long-term side effects in children. anemia is the main side effect of the drug.
"My impression is that the rate of preterm delivery in HIV-positive women with no therapy is high in general," Mofenson explains with regard to the issue of premature births. "The rate among women receiving therapy is lower." Since advanced disease and low T-cell counts may also play a role in pregnancy complications, combination therapy can be beneficial, contributing to a healthy pregnancy by slowing HIV infection and preventing opportunistic infections. A California study of 37 HIV-positive women published in January found that protease inhibitor treatment appeared safe, prevented HIV transmission, and caused no birth defects in 32 newborns studied thus far.
For now, HIV-positive women who become pregnant before starting any anti-HIV drug regimens are encouraged to wait until after 14 weeks to begin protease inhibitors. Those already taking protease drugs when they get pregnant should thoroughly discuss the risks and benefits of their current regimen with their doctors. For updates, contact the Antiretroviral Pregnancy Registry at (800) 722-9292 ext. 38465.
Experts continue to suggest that all pregnant women, regardless of their drug regimen, should take AZT to reduce the risk of perinatal transmission. Past studies show AZT used in late-stage pregnancy reduces maternal transmission by at least 70 percent. There's also encouraging new evidence that giving infants AZT within the first 48 hours after birth stops viral transmission-even when the mothers have not been treated. In a study of 454 babies, Dr. Nancy Wade of the New York State AIDS Institute found that infants treated within 48 hours of birth had only a 9.3 percent risk of infection-a huge improvement over the 25 percent transmission rate for untreated infants. "Postnatal treatment offers hope to a newborn whose mother's status wasn't known," says Dr. Wade. But for now she adds, "Initiating treatment during labor and after birth is still a second choice (to prenatal treatment)."
Consult your doctor for updates.
-EB
