title: Baseline CD4(+) T-cell counts and weighted background susceptibility scores strongly predict response to maraviroc regimens in treatment-experienced patients.
abstract: BACKGROUND
  Maraviroc-containing regimens are known to achieve virological suppression in many treatment-experienced patients. This study aimed to evaluate a more rigorous methodological approach to resistance-response analysis in large clinical studies and to better establish which subpopulations of patients were most likely to benefit from maraviroc by refining and extending previous subgroup analyses from the MOTIVATE studies.
  
  
  METHODS
  Individual weighted optimized background therapy (OBT) susceptibility scores were calculated by combining genotypic or phenotypic resistance testing with prior drug use information. Virological response (HIV-1 RNA<50 copies/ml at week 48) using each of these methods was compared with a commonly used method of counting active drugs. Baseline predictors of virological response, including weighted or unweighted scoring, maraviroc use, baseline CD4(+) T-cell count, HIV-1 plasma viral load and tropism, were assessed by logistic regression modelling.
  
  
  RESULTS
  Genotypic or phenotypic weighted methods were similarly predictive of virological response and better than counting active drugs. Weighted scoring and baseline CD4(+) T-cell count were the strongest predictors of virological response (P<0.0001): ≈70% of maraviroc patients with a weighted score ≥2 had a virological response, rising to ≈80% when the baseline CD4(+) T-cell count was ≥50 cells/mm(3).
  
  
  CONCLUSIONS
  Approximately 80% of patients with a CD4(+) T-cell count ≥50 cells/mm(3) receiving maraviroc with the equivalent of at least two fully active agents achieved HIV-1 RNA<50 copies/ml at week 48 in the MOTIVATE studies. Genotypic and phenotypic weighted scores were similarly predictive of virological response.
authors.affiliation: National Hemophilia Center, Tel Hashomer, Israel.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schapiro
authors.forename: Charles A B
authors.initials: CA
authors.lastname: Boucher
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: David A
authors.initials: DA
authors.lastname: van de Vijver
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.forename: Marilyn
authors.initials: M
authors.lastname: Lewis
authors.forename: Paul
authors.initials: P
authors.lastname: Simpson
authors.forename: Christophe
authors.initials: C
authors.lastname: Delogne
authors.forename: Lynn
authors.initials: L
authors.lastname: McFadyen
authors.forename: Douglass
authors.initials: D
authors.lastname: Chapman
authors.forename: Manos
authors.initials: M
authors.lastname: Perros
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Elna
authors.initials: E
authors.lastname: van der Ryst
authors.forename: Mike
authors.initials: M
authors.lastname: Westby
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D017326:Clinical Trials, Phase III as Topic; D003510:Cyclohexanes / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005838:Genotype; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D000077592:Maraviroc; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000821:virology; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D012367:RNA, Viral; D014230:Triazoles; D000077592:Maraviroc