title: 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.
abstract: 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.
authors.affiliation: Laboratoire de Virologie, CHU Necker, 149 rue de Sèvres, 75015 Paris, France. marie-laure.chaix@nck.aphp.fr
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Didier Koumavi
authors.initials: DK
authors.lastname: Ekouevi
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: François
authors.initials: F
authors.lastname: Rouet
authors.forename: Besigin
authors.initials: B
authors.lastname: Tonwe-Gold
authors.forename: Ida
authors.initials: I
authors.lastname: Viho
authors.forename: Laurence
authors.initials: L
authors.lastname: Bequet
authors.forename: Clarisse
authors.initials: C
authors.lastname: Amani-Bosse
authors.forename: Hervé
authors.initials: H
authors.lastname: Menan
authors.forename: Valériane
authors.initials: V
authors.lastname: Leroy
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: François
authors.initials: F
authors.lastname: Dabis
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D009000:Monocytes / Q000821:virology; D009154:Mutation / Q000235:genetics; D019829:Nevirapine / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010802:Phylogeny; D011237:Predictive Value of Tests; D011247:Pregnancy; D012367:RNA, Viral / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D019829:Nevirapine