8 Controversies in the Use of Nevirapine for the Prevention of Mother-to-Child Transmission James McIntyre Univ of the Witwatersrand, Chris Hani Baragwanath Hosp, Johannesburg, South Africa

Over the last decade, the successful identification and implementation of treatment strategies to prevent mother-to-child transmission of HIV (PMTCT) have reduced transmission rates to below 2% in the United States. Nevirapine, given as a single dose to the mother in labour with one dose to the infant, has provided the most feasible effective PMTCT intervention for low resource settings, confirmed in both clinical trials and program experience. Recent studies of combination therapy using antepartum zidovudine or zidovudine/lamivudine with peripartum nevirapine have demonstrated that transmission rates below 5% are also possible in Asia and Africa, and trials are in progress investigating nevirapine use to reduce breast milk transmission of HIV.

The single dose nevirapine regimen has provided the impetus to extend PMTCT programmes in a number of countries, but has also attracted a great deal of controversy, including allegations that it is a “western conspiracy” or a “second rate strategy” for poor countries, that the studies have been unethical or inadequate, that the drug is extremely toxic or that high rates of resistance will result.

Symptomatic liver toxicity and other major side effects have not been reported with the use of single dose nevirapine for PMTCT. The major disadvantage of the regimen is the risk of selection of nevirapine-resistant virus, and the potential impact on future pregnancies and on future treatment options. Detectable levels of NNRTI resistant virus are found six weeks post partum after single dose nevirapine in 20 – 50% of mothers and in around half of the HIV–infected infants. More sensitive techniques are demonstrating higher proportions of women with minority populations of resistant virus. The longer term implications of this are not fully understood, but remain concerning. Preliminary data from a study using a short postpartum course of zidovudine and lamivudine to reduce the selection of resistance have shown a reduction in detectable resistance to around 10%.

PMTCT interventions have been introduced in many countries, but it is estimated that current programmes still only reach 5% of all HIV-infected pregnant women. Antiretroviral regimens need to remain simple and feasible, while protecting the health of both mothers and children.