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Antimicrobial Agents and Chemotherapy, March 2007, p. 896-901, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00910-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Impact of Nevirapine (NVP) Plasma Concentration on Selection of Resistant Virus in Mothers Who Received Single-Dose NVP To Prevent Perinatal Human Immunodeficiency Virus Type 1 Transmission and Persistence of Resistant Virus in Their Infected Children

Université Paris Descartes, Faculté de Médecine, EA MRT 3620, Laboratoire de Virologie, Centre Hospitalier Universitaire (CHU) Necker Enfants Malades, Paris, France,¹ Unité INSERM 593, Institut de Santé Publique, Epidémiologie et Développement (ISPED), Université Victor Segalen, Bordeaux, France,² Projet ANRS DITRAME PLUS 1201/1202, Programme PACCI, CHU de Treichville, Abidjan, Côte d'Ivoire,³ Laboratoire de Pharmacologie Clinique, Hôpital Bichat Claude-Bernard, Paris, France,⁴ Centre de Diagnostic et de Recherches sur le SIDA (CeDReS), CHU de Treichville, Abidjan, Côte d'Ivoire,⁵ Programme MTCT-Plus, ACONDA, Abidjan, Côte d'Ivoire⁶

Received 24 July 2006/ Returned for modification 5 September 2006/ Accepted 7 December 2006

Nonnucleoside reverse transcriptase inhibitor resistance following the use of single-dose nevirapine (sdNVP) for the prevention of mother-to-child transmission (PMTCT) remains a concern. In the ANRS-1201/1202 Ditrame study, conducted in Abidjan, Côte d'Ivoire, a short-course regimen of zidovudine was associated with sdNVP for PMTCT. In this study, we estimate the frequency of NVP resistance and its relationship with NVP concentration in mothers. Genotypic resistance analysis was performed on mothers' plasma samples at week 4 postpartum (PP) and on human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMC) when an NVP resistance mutation was detected. The same tests were performed for the infected children at week 4, month 3, and month 12. Mothers' NVP plasma concentrations were measured at 48 h PP. Twenty-one (33%) of the 63 women selected had NVP-resistant (NVP-R) virus at week 4 PP. The median plasma NVP concentration was 598 ng/ml for the mothers without NVP-R virus compared to 851 ng/ml for the mothers harboring NVP-R virus (P = 0.014). NVP-R mutations were detected in the HIV DNA of 15/20 women. Plasma NVP-R mutations were detectable in 6 of 26 infected children at week 4. All 6 children had detectable NVP-R mutations in HIV DNA of PBMC. Blood samples taken at month 3 (1 child) and month 12 (1 child) revealed the persistence of NVP-R mutations in plasma and cells. Emergence of NVP-R virus in mothers is strongly correlated with a high level of plasma NVP concentration, owing to a prolonged postpartum period of viral replication under NVP selective pressure. The follow-up of the cohort demonstrates the prolonged archive of resistant virus.

Published ahead of print on 18 December 2006.