title: Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique.
abstract: BACKGROUND
  Single-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT.
  
  
  OBJECTIVE
  To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique.
  
  
  METHODS
  One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012) at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/μL (Viroseq). Sequencing was performed with ABI 3100 (Applied Biosystems). Logistic regression modelling was undertaken to identify the factors associated with NVP RAM.
  
  
  RESULTS
  Seventy-nine children had their samples genotyped. Their median age was 7.0 (3-12) months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs) for PMTCT. ARV RAM were detected in 43 (54.4%) of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93-186.34) and with mother's CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02-9.32). In the multivariable analysis the mother's exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33-253.66).
  
  
  CONCLUSIONS
  We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers' exposure to PMTCT significantly increased the risk of NVP RAM.
authors.affiliation: Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Antunes
authors.affiliation: Departamento de Medicinas, Instituto Nacional de Saúde, Hospital Central de Maputo, Maputo, Mozambique.
authors.forename: Pereira
authors.initials: P
authors.lastname: Zindoga
authors.affiliation: Laboratório de Microbiologia Clínica e Biologia Molecular, Serviço de Patologia Clínica, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal.
authors.forename: Perpétua
authors.initials: P
authors.lastname: Gomes
authors.affiliation: Saúde da Comunidade, Faculdade de Medicina da Universidade Eduardo Mondlane, Maputo, Mozambique.
authors.forename: Orvalho
authors.initials: O
authors.lastname: Augusto
authors.affiliation: Plataformas Tecnológicas, Plataforma de Virologia Molecular, Instituto Nacional de Saúde, Maputo, Mozambique.
authors.forename: Isabel
authors.initials: I
authors.lastname: Mahumane
authors.affiliation: Clinical Data Unit, Eurotrials Scientific Consultants, Lisboa, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Veloso
authors.affiliation: Clínica Universitária de Doenças Infecciosas e Parasitárias, Faculdade de Medicina de Lisboa, Lisboa, Portugal.
authors.forename: Emília
authors.initials: E
authors.lastname: Valadas
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, Leuven, Belgium.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Camacho
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005814:Genes, Viral; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007223:Infant; D017053:Infection Control; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D009073:Mozambique; D019829:Nevirapine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine