title: High Rates of Baseline Drug Resistance and Virologic Failure Among ART-naive HIV-infected Children in Mali.
abstract: BACKGROUND
  Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children <10 years of age initiating ART in Mali.
  
  
  METHODS
  Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance.
  
  
  RESULTS
  One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P < 0.001) and protease inhibitor-based ART initiation among children without baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use.
  
  
  CONCLUSIONS
  Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.
authors.affiliation: From the *Department of Pediatrics, Division of Infectious Diseases, University of Washington, and †Seattle Children's Hospital, Seattle, Washington; ‡Unité d'Epidémiologie Moléculaire de la Résistance du VIH aux ARV, SEREFO, §University of Sciences, Techniques and Technologies of Bamako, and ¶Department of Pediatrics, University Hospital Gabriel Touré, Bamako, Mali; ‖Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois; **Seattle Children's Research Institute, Children's Core for Biomedical Statistics, Seattle, Washington; ††Department of Virology, Sorbonne Université, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, ‡‡Department of Pharmaco-Toxicology, APHP, Bichat-Claude Bernard Hospital, and §§Paris Diderot University, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France; and ¶¶Department of Pediatrics, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Crowell
authors.forename: Almoustapha I
authors.initials: AI
authors.lastname: Maiga
authors.forename: Mariam
authors.initials: M
authors.lastname: Sylla
authors.forename: Babafemi
authors.initials: B
authors.lastname: Taiwo
authors.forename: Niaboula
authors.initials: N
authors.lastname: Kone
authors.forename: Assaf P
authors.initials: AP
authors.lastname: Oron
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Ban
authors.initials: B
authors.lastname: Traore
authors.forename: Djeneba B
authors.initials: DB
authors.lastname: Fofana
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Ellen G
authors.initials: EG
authors.lastname: Chadwick
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D008302:Mali; D011446:Prospective Studies; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents