title: Population-based V3 genotypic tropism assay: a retrospective analysis using screening samples from the A4001029 and MOTIVATE studies.
abstract: BACKGROUND
  The MOTIVATE-1 and 2 studies compared maraviroc (MVC) along with optimized background therapy (OBT) vs. placebo along with OBT in treatment-experienced patients screened as having R5-HIV (original Monogram Trofile). A subset screened with non-R5 HIV were treated with MVC or placebo along with OBT in a sister safety trial, A4001029. This analysis retrospectively examined the performance of population-based sequence analysis of HIV-1 env V3-loop to predict coreceptor tropism.
  
  
  METHODS
  Triplicate V3-loop sequences were generated using stored screening plasma samples and data was processed using custom software ('ReCall'), blinded to clinical response. Tropism was inferred using geno2pheno ('g2p'; 5% false positive rate). Primary outcomes were viral load changes after starting maraviroc; and concordance with prior screening Trofile results.
  
  
  RESULTS
  Genotype and Trofile results were available for 1164 individuals with virological outcome data (N = 169 non-R5 by Trofile). Compared with Trofile, V3 genotyping had a specificity of 92.6% and a sensitivity of 67.4% for detecting non-R5 virus. However, when compared with clinical outcome, virological responses were consistently similar between Trofile and V3 genotype at weeks 8 and 24 following the initiation of therapy for patients categorized as R5.
  
  
  CONCLUSIONS
  Despite differences in sensitivity for predicting non-R5 HIV, week 8 and 24 week virological responses were similar in this treatment-experienced population. These findings suggest the potential utility of V3 genotyping as an accessible assay to select patients who may benefit from maraviroc treatment. Optimization of the predictive tropism algorithm may lead to further improvement in the clinical utility of HIV genotypic tropism assays.
authors.affiliation: BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: McGovern
authors.forename: Alexander
authors.initials: A
authors.lastname: Thielen
authors.forename: Theresa
authors.initials: T
authors.lastname: Mo
authors.forename: Winnie
authors.initials: W
authors.lastname: Dong
authors.forename: Conan K
authors.initials: CK
authors.lastname: Woods
authors.forename: Douglass
authors.initials: D
authors.lastname: Chapman
authors.forename: Marilyn
authors.initials: M
authors.lastname: Lewis
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.forename: Jayvant
authors.initials: J
authors.lastname: Heera
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000502:physiology; D015658:HIV Infections / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D000077592:Maraviroc; D012367:RNA, Viral / Q000235:genetics; D015728:Receptors, HIV / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014230:Triazoles / Q000008:administration & dosage*; D019562:Viral Load; D056189:Viral Tropism / Q000235:genetics* / Q000502:physiology
chemical_list: D003510:Cyclohexanes; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral; D015728:Receptors, HIV; D014230:Triazoles; D000077592:Maraviroc