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Original Article
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Volume 351:229-240 July 15, 2004 Number 3
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Intrapartum Exposure to Nevirapine and Subsequent Maternal Responses to Nevirapine-Based Antiretroviral Therapy
Gonzague Jourdain, M.D., Nicole Ngo-Giang-Huong, Pharm.D., Ph.D., Sophie Le Coeur, M.D., Ph.D., Chureeratana Bowonwatanuwong, M.D., Pacharee Kantipong, M.D., Pranee Leechanachai, Ph.D., Surabhon Ariyadej, M.D., Prattana Leenasirimakul, M.D., Scott Hammer, M.D., Marc Lallemant, M.D., for the Perinatal HIV Prevention Trial Group

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ABSTRACT

Background A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown.

Methods We randomly assigned 1844 women in Thailand who received zidovudine during the third trimester of pregnancy to receive intrapartum nevirapine or placebo. In the postpartum period, 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapine-containing antiretroviral regimen. Plasma samples were obtained 10 days post partum and analyzed for resistance mutations. Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of therapy and three and six months thereafter.

Results After six months of therapy, the HIV-1 RNA level was less than 50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine, as compared with 68 percent of the women who had not received intrapartum nevirapine (P=0.03). Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations were K103N, G190A, and Y181C. Among the women who had received intrapartum nevirapine, viral suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of those without resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53 log10 copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated with virologic failure. After six months of therapy, there was no significant difference between groups in the CD4 count (P=0.65).

Conclusions Women who received intrapartum nevirapine were less likely to have virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen. Our data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral therapy for mothers.


Source Information

From the Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston (G.J., N.N.-G.-H., M.L.); the Perinatal HIV Prevention Trial Group, Institut de Recherche pour le Développement, Paris, and Chiang Mai, Thailand (G.J., N.N.-G.-H., S.L., M.L.); the Institut National d'Etudes Démographiques, Paris (S.L.); the Ministry of Public Health, Bangkok, Thailand (C.B., P.K., S.A., P. Leenasirimakul); Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand (P. Leechanachai); and Columbia University College of Physicians and Surgeons, New York (S.H.).

Address reprint requests to Dr. Jourdain at PHPT-IRD54, 29/7-8 Samlan Rd., Soi 1 Prasing Muang, Chiang Mai 50200, Thailand, or at gonzague{at}phpt.org.

Full Text of this Article


Related Letters:

Nevirapine plus Zidovudine to Prevent Mother-to-Child Transmission of HIV
Herzmann C., Karcher H., Goulder P. J.R., Blanckenberg N., Dong K., Lallemant M., Jourdain G., Le Coeur S.
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N Engl J Med 2004; 351:2013-2015, Nov 4, 2004. Correspondence

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