title: CCR5 antagonists:  a therapeutic option in HIV-1 perinatally infected children experiencing virologic failure?
abstract: OBJECTIVE
  The risk of virologic failure and selection of resistant strains remains a challenge in HIV-1 perinatally infected children. HIV-1 coreceptor usage was determined in HAART-failing children followed in Necker Hospital (Paris, France) in order to estimate the proportion of these patients who may benefit from CCR5-antagonists therapy.
  
  
  METHODS
  HIV-1 coreceptor usage was determined with the SVM(Geno2pheno10%) algorithm in 51 children with virologic failure after a median treatment exposure of 7.8 years.
  
  
  RESULTS
  CXCR4-tropic strains were found in 31.4% of the patients. CXCR4 usage was associated with high HIV-1 DNA (P=0.01), old age (P=0.02), long ART cumulative exposure (P=0.006), and previous exposure to high number of different drugs (P=0.03) and ART combinations (P=0.03) in univariate analysis. Selection of resistant viruses and current exposure to a darunavir-based HAART tended to be more frequent in the CXCR4 group compared with the children infected with CCR5-tropic strains (P=0.06). In multivariate analysis, CXCR4 usage was exclusively correlated with HIV-1 DNA (P=0.03), which accurately reflects the cumulative exposure to viral replication over the whole duration of HIV infection.
  
  
  CONCLUSIONS
  Two-thirds of HAART-failing children could benefit from CCR5 antagonists-based strategies, even in case of triple-class virologic failure. Such therapy should be discussed more appropriately at early stages of infection, when CCR5-tropic strains are most frequently isolated. However, before considering such strategies, further studies are needed to evaluate the efficacy and the tolerability of CCR5 antagonists in this pediatric population.
authors.affiliation: Université Paris-Descartes EA 3620, Sorbonne Paris Cité, Paris, France. pierre.frange@nck.aphp.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.forename: Nelly
authors.initials: N
authors.lastname: Briand
authors.forename: Florence
authors.initials: F
authors.lastname: Veber
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fenoel
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D065100:CCR5 Receptor Antagonists; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics* / Q000276:immunology; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D010297:Paris; D019713:Receptors, CCR5 / Q000276:immunology; D019718:Receptors, CXCR4 / Q000276:immunology / Q000302:isolation & purification*; D017211:Treatment Failure; D019562:Viral Load; D056189:Viral Tropism
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D019713:Receptors, CCR5; D019718:Receptors, CXCR4