Progress in Preventing Perinatal Transmission of HIV

Despite the excitement surrounding the results of ACTG 076 and initial reports of decreased transmission in some populations, preventing perinatal transmission has remained a formidable challenge. Some of the problems include translating the recommendations into practice, determining whether all three components of ZDV therapy are necessary, finding the most appropriate therapy for ZDV pre-treated women, and learning whether newer agents are safe and more effective. Most important, perhaps, is finding solutions that can be applied in developing countries, where up to 1000 HIV-infected babies are born each day.

Several papers cast some light on a few of these questions. Dr. Susan Fiscus from University of North Carolina at Chapel Hill presented continuing data on the success of a program to implement voluntary prenatal HIV testing and ZDV use for the state of North Carolina (Abstract #379). In 1995 and 1996 respectively, 84% and 93% of pregnant HIV-infected women were identified and offered ZDV. The transmission rate dropped from 21% in 1993 to 7.6% in 1996. Of 18 HIV infected children born in 1996, 14 were in women not treated with ZDV. The most common reason for not receiving ZDV was that the woman was never counseled. They reviewed the charts to determine whether the mother had received oral ZDV during pregnancy, IV therapy during labor, and whether the infant took oral ZDV. Although she advised caution based on small numbers in some groups, it appeared that maternal treatment was the most important component, and that ZDV offered little benefit to the infant if the mother was not treated.

Several other studies reported progress in reducing transmission by implementing the PHS recommendations including studies from Wisconsin, and a report of slower but gratifying progress (against impressive odds) in New York City.

Stephanie Blanche presented data from the French nationwide cohort study (Abstract #340). In France, physicians are legally obligated to offer HIV testing during pregnancy, but testing is voluntary. Less than 5% of pregnant women refuse testing and 88-90% are treated with ZDV. Transmission in France dropped dramatically beginning in late 1994 to only 5%. The efficacy of ZDV was similar across CD4 counts and in women delivering vaginally or by C section. However, among women who were pretreated with ZDV, there appeared to be little or now benefit. It seems likely that this is due to resistance, however, resistance studies are not yet available. This highlights the urgent need to explore other agents. An interesting poster presented the results of a preliminary study of the pharmacokinetics and safety of ZDV and 3TC in pregnant women and their infants. Pregnancy did not alter levels in the mothers, therapeutic levels were achieved in the infants with oral treatment, and no unusual toxicities were observed. This is encouraging, but similar studies are urgently needed with other nucleoside combinations for ZDV intolerant women (such as ddI/D4T) and with protease inhibitor containing combinations

In Vancouver, preliminary data was presented that nevaripine could maintain prolonged therapeutic levels in a new born after a single oral dose taken by the mother. Dr. Mark Mirochnick presented a paper at the 4th retrovirus conference (abstract 723) reporting the safety and pharmacokinetics of nevaripine given as a single oral 200 mg dose when the mother began labor, followed by a single oral dose of 2 mg/kg given to the infant at about 48 hours of life. All of the mothers maintained serum levels that would be predicted to be effective throughout labor and until 48 hours after birth (median 1240 ng/ml). All of the children had therapeutic levels for the first 48 hours of life due to the maternal dose, and following a single dose (median trough dose 541 ng/ml, range 141 to 768), they maintained adequate levels up to day 7 of life (median day 7 level 215 ng/ml). There were no toxicities observed. ACTG 316 is a large randomized trial which will evaluate whether adding nevarapine during labor to standard zidovudine therapy can further reduce maternal transmission below the current level of 5-8%. Additional potential benefits might be a less expensive regimen and one which could give some protection to women and their infants with resistant virus, or inadequate prenatal care.