Published online September 5, 2006
PEDIATRICS Vol. 118 Supplement August 2006, pp. S50-S51 (doi:10.1542/peds.2006-0900EEEE)
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Emergence of Drug Resistant HIV-1 After Intrapartum Administration of Single-Dose Nevirapine Is Substantially Underestimated

Joseph A. Church, MD

Los Angeles, CA

ABSTRACT

PURPOSE OF THE STUDY.: An inexpensive, effective regimen to prevent perinatal HIV transmission in the developing world is highly desirable. Nevirapine, a nonnucleoside reverse transcriptase inhibitor, seems to provide such an intervention. However, drug-resistance mutations have been identified in up to 40% of women shortly after they received a single intrapartum nevirapine dose as part of a transmission-prevention strategy. This study was undertaken to reexamine the incidence of drug-resistant HIV-1 after single-dose nevirapine.

STUDY POPULATION.: Fifty South African women infected with HIV subtype C.

METHODS.: Sensitive, real-time polymerase chain reaction assays were sequentially performed for nonnucleoside reverse transcriptase inhibitor–resistance mutation, K103N and Y181C.

RESULTS.: Resistance mutations emerged in 65% of women after a single dose of nevirapine.

CONCLUSIONS.: Single-dose nevirapine as used in the developing world for prevention of perinatal HIV transmission results in the development of resistance mutations in a very high percentage of women who receive this intervention.

REVIEWER COMMENTS.: Although single-dose nevirapine has been successfully implemented as a strategy to prevent perinatal HIV transmission, it is increasingly apparent that the women who are treated with this regimen more often than not develop resistance mutations to nevirapine. The clinical implications are clear: Will nevirapine work for future perinatal interventions for individual women with drug-resistance mutations? Will women with these drug-resistance mutations fail to respond to nevirapine as part of a highly active retroviral therapy intervention when they need treatment for their own HIV disease? In the same issue of The Journal of Infectious Diseases, Flys et al (J Infect Dis. 2005;192:24–29) demonstrated that drug-resistance variants of HIV may persist for >1 year in this situation. In addition, Lee et al (J Infect Dis. 2005;192:1260–1264) showed that women who developed drug-resistant HIV after exposure to single-dose nevirapine shed drug-resistant HIV in their breast milk. This increases the risk of transmission of resistant virus to uninfected infants. Together, these studies demonstrate that single-dose nevirapine, although an effective strategy for reducing maternal-child transmission of HIV, also predisposes treated women to the development of drug-resistant virus as well as the potential for transmitting drug-resistant virus to their infants via breastfeeding.

Johnson JA, Li JF, Morris L, et al. J Infect Dis. 2005;192:16–23[CrossRef][ISI][Medline]