New Tests Would Help Lower Perinatal Transmission
In pregnancy, zidovudine should still be used whenever possible as a component of HAART regimens. Although it is similar in many ways to other nucleoside reverse transcriptase inhibitors, it has the advantage of demonstrated efficacy in preventing perinatal transmission.
If you don't see a substantial number of HIV-infected women, or if you don't keep up with the ever-expanding body of literature on antiretroviral drugs and patient management, I would advise comanaging your patient with an HIV specialist.
The obstetrician's key role is to ask the consultant what he or she would recommend if the patient were not pregnant, and then to take the lead in evaluating the drugs' benefits, toxicities, and risks. Obstetricians—with their dual roles of optimizing the health of the mother and preventing transmission of the virus to the child, in that order of priority—should be the ones to modify the regimen if necessary.
We often use category C drugs during pregnancy if we know that a drug is much more effective than a category B drug. However, specialists in other disciplines might recommend category B drugs, not because they are better but because of those specialists' unfamiliarity with the care of pregnant women and their fear of using category C drugs. We should be the ones to make that call, and should work with the HIV specialist in balancing efficacy and fetal safety.
The HIV specialists, on the other hand, are going to know all the ins and outs about drug combinations, about acceptable rates of viral load decrease, and about dosing schedules and other logistical details.
In general, the use of two nucleoside reverse transcriptase inhibitors along with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor is recommended. It also is often useful to choose a regimen that spares one class of antiretroviral agents in case resistance develops. There are choices within each of the three drug categories, but there also are certain medications that should not be used in combination because of overlapping toxicities or diminished efficacy.
There are also certain potential perinatal risks. Nevirapine, for instance, can cause fulminant liver disease in women who have CD4 counts greater than 250 cells/mm
Treatment with efavirenz, for example, should be avoided during the first trimester because the drug has been associated with severe central nervous system anomalies. Overall, it's important to recognize and tell patients that we do not have long-term outcome data on the use during pregnancy of any of the available antiretroviral drugs.
The number of HAART regimens continues to increase, and there may be new reports of problems, so in addition to consulting with HIV specialists, obstetricians should also make use of the Public Health Service's Web site (
www.aidsinfo.nih.gov/guidelines
Prevention of Resistance
Once therapy is underway, viral loads should be checked every month until the viral load is undetectable. At that point, monitoring should be done every 2–3 months. If the viral load is not dropping or does not become undetectable within 6 months, a decision about new therapy will have to be made.
Before therapy is stopped, however, your patient must undergo resistance testing—a practice that has become a standard component of HIV care, mainly for identifying therapies that should not be used in the new regimen.
If you stop therapy first and draw blood just a week later, the wild-type virus (the nonmutant strain) may have overgrown a minority mutant strain, and the resistant virus may not be detected. You must draw blood before discontinuing therapy.
Also remember that second regimens do not work as well as first regimens, so it is important to do everything possible to prevent nonadherence. Patients who are only intermittently adherent—who have intermediate drug levels—are more likely to develop resistance.
Be sure to explain at the start that it is critical for the patient to be committed to therapy and to take drugs in a timely fashion. And if a patient develops nausea and vomiting, have her stop her drug regimen until the symptoms subside.
Mode of Delivery
As a rule, women who have scheduled a cesarean delivery before the onset of labor and before rupture of membranes have a lower rate of perinatal HIV-1 transmission. However, for a patient whose viral load is very low, there really is no evidence that scheduled cesarean delivery can lower the risk of transmission.
In addition, there is some preliminary evidence to support the notion that even some patients whose viral load is not that low—plasma HIV-1 RNA levels higher than 1,000 copies/mL—may not benefit from cesarean delivery if they are being given HAART. Those data remain to be confirmed.
