Mother Knows Best
More choices than ever for pregnant women
What a difference a year makes. In just about the time it takes for infants to start walking, cautious steps prove you can take combination HIV therapy during pregnancy and remain on solid ground. Two years ago, reports of unusual birth defects and high rates of premature delivery among women raised the alarm about taking protease inhibitors during pregnancy. But as more women choose to start or stay on combo regimens while pregnant, the safety picture is getting better, not worse. A review of nearly 3,500 pregnancies found that women who took antiretrovirals were not at increased risk for premature delivery. And while PIs and other HIV drugs have been linked to rare birth defects, doctors agree that the benefits of delivering an HIV-negative child outweigh the theoretical risks posed by these different drugs. That's not to say they've got everything figured out. Current federal guidelines (available online at www.hivatis.org) present four different pregnancy scenarios, each with its own set of treatment choices. There are millions of potential pregnancy scenarios-one for each woman with HIV who chooses to have a child. Only the most basic information applies to all. The best approach is one that integrates HIV care into prenatal care. The first step is getting tested for HIV as soon as you know you're pregnant. Next, find a medical team you trust and can talk to. Consider what type of treatment you want to take for the baby and yourself. The guidelines suggest starting triple-combination HIV therapy after the first trimester, when the drugs are least likely to affect fetal development.

When it comes to drugs, however, the choice is yours. "I don't think there's any compelling information about a specific regimen being better than any other," says Dr. Kathleen Squires, director of women's activities at the University of Alabama at Birmingham, who specializes in HIV. Instead, it's important to choose a combo you can stick to and afford. That may also mean taking drug side effects into account. For example, Norvir often causes nausea and can upset the stomach, and might make routine morning sickness that much worse. Taking Crixivan can cause high bilirubin levels in infants. So far, there have been no problems treating the condition, Squires says, so there's no need to switch if a woman is on a Crix-containing regimen that's working. Experts emphasize that the bottom line is viral control. That can be a real challenge for women who've developed resistance and are on their second or third regimen. Consider resistance testing (see below) and the available arsenal of prevention techniques to maximize your chances of delivering an HIV-negative baby.

It's also important to make a postdelivery treatment plan. Some women's adherance drops dramatically after pregnancy. It's better to stop all drugs than to let motherhood and the rest of life interfere with meds. There's also the risk of transmission during breast-feeding, so discuss your concerns with your doctor.

ABCs of AZT
No matter what other drugs you're taking, pediatric experts recommend adding AZT to every pregnant woman's regimen. Nevirapine (see below) can also be used at time of delivery. That's because both of these drugs cross the placenta and inhibit viral replication in the womb.

Doctors often know that a drug works without understanding exactly how or why. That's certainly the case with AZT, the original weapon against HIV and perinatal transmission. As time goes on, we're getting a better picture of how AZT works. For one thing, the drug is stockpiled in the blood of the umbilical cord, building up to high concentrations that help control the virus in the blood the mother supplies to the fetus. AZT also makes its way into DNA. In January, federal researchers showed that in a study of rhesus monkeys who received AZT during labor, the drug incorporated itself into fetal DNA. (This is a similar dose to what a woman who receives HIV drugs only during delivery might experience.) The news isn't that surprising, since AZT belongs to a class of drugs that's designed to elbow its way inside genetic material. But the fact that the drug turned up in fetal monkey livers, lungs, hearts, and brain cells after just three hours of maternal exposure is worrisome. Some researchers say changes in DNA open the door to cellular mutations and even cancer. These findings offer yet another argument for close, long-term follow-up of both positive and negative children born to women treated with AZT and other "nukes."

GETTING TO KNOW NEVIRAPINE
Nevirapine is the newest addition to the family of perinatal transmission prevention tools. Last year brought encouraging news that an inexpensive single dose of nevirapine to both mother and child lowered transmission rates significantly. That's especially good news for women in sub-Saharan Africa and other developing areas of the world where the cost of six weeks of AZT, let alone ongoing treatment with combination therapy, is simply too high.

What about the United States? Here, women have access to care, albeit uneven. It's too early to say whether late-stage nevirapine will be a useful addition to other regimens. But there are risks. The drug has an extremely long half-life, allowing it to stay in the blood for more than seven days, opening the door for resistance. "There's a risk of resistance occurring very rapidly if viral replication is not completely suppressed," says Dr. Lisa Frenkel, a pediatrician and resistance expert at the University of Washington. An ongoing study will test whether one dose to the mom in labor and one dose to the infant adds protection. For now, Frenkel says, she would recommend it only for women whose viral load count is over 50 copies. The currently recommended regimen continues to be AZT beginning after the first trimester plus whatever antiretroviral therapy a pregnant women has chosen.

RESISTANCE IS USEFUL
Resistance testing, that is. The list of reasons why pregnant women should get their hands on these high-tech tests just keeps getting longer. For one thing, drug-resistant virus doesn't cause your viral load count to go up right away. It's possible to have partial or low-level resistance to some of the drugs in your regimen even when viral load appears to be under control. In this case, it's only a matter of time before viral rebound occurs-exactly what you want to avoid during pregnancy. Because of this, experts such as resistance specialist Dr. Victoria Johnson at the University of Alabama at Birmingham recommend that these tests be given to every pregnant woman, even if a given regimen appears to be working. It's also possible to carry resistant virus if you've never been on therapy at all. "Among newly infected individuals, there is a small but substantial population that is infected with resistant virus," says Frenkel. The January 1998 federal guidelines on perinatal transmission discuss resistance testing for untreated pregnant women. This recommendation has not yet been updated, but some experts suggest it should be expanded to include all women with detectable viral loads. This makes it more important than ever that private insurers, AIDS Drug Assistance Programs (ADAPs), and Medicaid help put these expensive tests within women's reach. Ask your doctor for more information.

-EB