February 27, 2002
The use of a single dose of nevirapine is the most important advance in the prevention of mother-to-child transmission (MTCT) since the original trial of AZT. In this landmark trial in Uganda, a single dose for the mother at the onset of active labor followed by a single dose for the infant was twice as effective at preventing MTCT as an ultra short course of AZT.
That ultra short course of AZT itself was recently shown to be as effective. The World Health Organization recommended a four-week pre-delivery course of AZT (known as the Thai regimen) which reduces transmission by 50 percent. While the emergence of resistance in about 19 percent of women is an important issue with nevirapine use, this inexpensive and life-saving intervention is being implemented in many areas of Africa. At a symposium on antiretroviral therapy in the developing world, Dr. Catherine Wilfert described a program funded by the Elizabeth Glaser Pediatric AIDS Foundation which has already funded 30 programs around the world.
In this paper, Dr. Fowler examined how the mother's health influenced the utility of nevirapine in the HIVNET 012 study, including viral load and CD4 count. These are important markers, since the mother's viral load at delivery is one of the most important predictors of whether a baby will be infected, and CD4 count is also predictive. This is true in developing countries as well as in more developed countries.
Not surprisingly, viral load was a strong predictor of the risk of transmission. Among women with viral loads of less than 500 copies, no infants in either the nevirapine or the AZT group were infected. Among the women with more than 50,000 copies, 45 percent of the children of mothers in the AZT group were infected by 18 months of age, compared to 25 percent of those in the nevirapine group. Similarly, among mothers with less than 200 CD4 cells, the AZT treated mothers had a 55 percent rate of infection at 15 months compared to 32 percent.
Recall that this is a breast-fed population in Uganda, and a significant number of children became infected after birth through breast feeding. This makes it particularly important that a protective effect continued to be seen out to 18 months of life.
Given the simplicity of the regimen, one might worry that it would fail among women with very high viral loads. However, the regimen was as effective in the highest risk group as it was for all the women. In fact, it is among these women that the greatest benefit will be seen.
In the question and answer session, Dr. Fowler was asked whether the risk of developing nevirapine resistance was higher among those with high viral load. She responded that it was.
While the benefits of nevirapine monotherapy in pregnant women must be balanced against the risk that the mother might develop nevirapine resistance which might limit her future treatment options, the best answer is to prevent both MTCT and the emergence of resistance, and preserve the mother's health.
In the developed world, this can be achieved by using fully suppressive regimens for the mother. In the developing world, an interim strategy may be the use of combination therapy for short courses. An example might be to begin AZT with or without 3TC and nevirapine at the onset of labor, followed by one week of AZT. Ultimately, most experts agree that we must move toward continuing treatment for the mother's health after delivery. This will lead to an uninfected child with a healthy mother. Several studies have shown that even if the baby is uninfected, it is far more likely to die if the mother becomes seriously ill.
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