Along with increasing usage of ZDV, two other trends have developed. One, an increasing number of HIV-infected pregnant women are receiving highly active antiretroviral therapy (HAART), and there appears to be an emerging consensus that a pregnant woman should be treated in the same manner as she would have if she wasn't pregnant, i.e. therapy should be continued, particularly if the woman's HIV viral load is undetectable. This concept has included the recommendation that, whatever the rest of the HAART regimen, ZDV should be continued, since it is the one drug that has shown a preventive effect in MCT. A small, but growing body of information suggests that women with an undetectable viral load rarely, if ever, transmit HIV to their infants. The second trend is toward an increasing number of elective cesarean-section deliveries, following the demonstrated benefit of this mode of delivery. The French group studying this question says that only in ZDV recipients has that benefit been shown.
Despite the information outlined above, USPHS guidelines still recommend ZDV use by mother and infant for MCT prevention in pregnancy. Whether or not that recommendation will be altered in light of the information on undetectable viral load, i.e. whether any HAART regimen resulting in such a viral load is similarly effective in reducing MCT, remains to be seen. New USPHS guidelines, including considerations of undetectable viral load, cesarean-section, nevirapine use, and initial treatment of women who become HIV-infected during pregnancy, are expected in the next few months. We will always need to emphasize that an essential part of any plan to reduce HIV MCT is HIV testing, and, even before that, encouragement of adequate prenatal care by all pregnant women.
However, 90% of all new infections of HIV are in the undeveloped world. Sub-Saharan Africa has one of the highest mother-to-infant transmission rates. It is estimated that in 1999, there were as many as 700,000 infants who contracted HIV from their mothers worldwide; over 200,000 of these cases resulted from transmission via breast milk.
The use of ZDV, as in the 076 protocol, and elective C-section are not effective in the undeveloped world because these strategies are too expensive and impractical. These strategies require prenatal care early on in pregnancy, the proper use and storage of costly medications, and no breast-feeding. Many women in undeveloped countries present late for prenatal care, and since breast milk is a baby's only safe source of nutrition in Africa, it is a necessity.
A recent study done in Uganda, Africa took into account these issues of cost, practicality and breast-feeding. This study of the prevention of perinatal transmission of HIV in a breast-feeding population is called HIVNET 012. HIVNET 012 enrolled 626 women and randomly assigned them to receive one of two regimens. The first regimen consisted of a single 200 mg nevirapine tablet taken by the mother at the onset of labor, followed by an oral dose of nevirapine suspension given to the baby at 72 hours of life or at discharge from the hospital (whichever was earlier). The second regimen consisted of a short course of ZDV twice daily for 7 days after birth.
In this breast-feeding population, the rate of HIV transmission from mother to baby in the nevirapine group was 13.1% compared to 25.1% in the short course ZDV group.
Adverse events were low, and there were only six adverse events that could have possibly, but unlikely, been related to the study drugs. Four events were in the ZDV group and two in the nevirapine group. These events included Sudden Infant Death Syndrome, transient tachypnea, birth asphyxia, and pneumonia in the ZDV group. In the nevirapine group, events were transient respiratory distress and nonmacerated birth. All other adverse effects included rash, anemia and abnormal lab values, and these were similar in each group.
In summary, the use of nevirapine to prevent perinatal HIV transmission in the undeveloped, breast-feeding population is simple, practical, low-cost and effective. It can be used in women who present into care close to term, and it can be used in the breast-feeding population. Nevirapine is lipophilic, which makes it available in breast milk, potentially preventing transmission via that route.
The U.S. cost of nevirapine is $4/day, where the cost of ZDV in the 076 protocol is more than $200/day per mother/infant pair for the drugs alone, and this is taking into account the 75% reduction rate in ZDV prices for Africa announced by Glaxo Wellcome. This is an extremely high per-capita cost.