title: High prevalence of X4/DM-tropic variants in children and adolescents infected with HIV-1 by vertical transmission.
abstract: BACKGROUND
  We studied HIV coreceptor tropism in vertically HIV-infected children and adolescents with the objective of predicting the proportion of children and adolescents that could be treated with CCR5 (R5) antagonists.
  
  
  METHODS
  One hundred eighteen multidrug-resistant pediatric patients (36 children and 82 adolescents) were enrolled in a cross-sectional study. Viral tropism was assessed using the new phenotypic HIV-1 tropism coreceptor assay information and Trofile.
  
  
  RESULTS
  Of 118 antiretroviral-experienced HIV-infected children and adolescents, 49 (57.0%) had dual-tropic and 20 (23.3%) had X4-tropic viruses by tropism coreceptor assay information testing. Only 17 (19.7%) showed R5-tropic variants. HIV-1 coreceptor usage was not detectable in 32 of 118 (27%) patients. Among 24 children and 62 adolescents with tropism coreceptor assay information results, 17 (70.8%) children and 51 (82.2%) adolescents showed viruses with dual-tropic or X4-tropic variants. Additionally, Trofile (ES) was performed in 42 of 118 patients with HIV-1 RNA > 1000 copies/mL. No patient showed X4-tropic variants; dual-tropic viruses were observed in 12 (28.6%) patients. In 6 (14.3%) patients, HIV tropism could not be determined. X4-tropic variants were more common in children (P = 0.031). CD4 T cell percentage was significantly lower in children (P = 0.011) and adolescents (P = 0.027) with R5-tropic viruses than in those with X4-tropic viruses.
  
  
  CONCLUSIONS
  The presence of X4-tropic variants in more than 80% of our cohort of antiretroviral-experienced children and adolescents with vertical HIV-1 infection indicates a very limited role for CCR5 antagonists as part of salvage regimens for highly treatment-experienced vertically HIV-1-infected patients with extensive antiretroviral drug resistance and limited treatment options.
authors: Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors: Verónica
authors: V
authors: Briz
authors: Dolores
authors: D
authors: García
authors: Gema
authors: G
authors: Méndez-Lagares
authors: Ezequiel
authors: E
authors: Ruiz-Mateos
authors: Miguel
authors: M
authors: de Mulder
authors: David
authors: D
authors: Moreno-Pérez
authors: M Luisa
authors: ML
authors: Navarro
authors: Juan A
authors: JA
authors: León-Leal
authors: M Isabel
authors: MI
authors: de José
authors: José T
authors: JT
authors: Ramos
authors: M José
authors: MJ
authors: Mellado
authors: M Isabel
authors: MI
authors: González-Tomé
authors: Manuel
authors: M
authors: Leal
authors: M Angeles
authors: MA
authors: Muñoz-Fernández
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D002648:Child; D003430:Cross-Sectional Studies; D003510:Cyclohexanes / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D000077592:Maraviroc; D015995:Prevalence; D015728:Receptors, HIV / Q000037:antagonists & inhibitors; D016879:Salvage Therapy / Q000379:methods; D014230:Triazoles / Q000627:therapeutic use; D056189:Viral Tropism
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D015728:Receptors, HIV; D014230:Triazoles; D000077592:Maraviroc