title: Use of cellular HIV DNA to predict virologic response to maraviroc: performance of population-based and deep sequencing.
abstract: BACKGROUND
  A tropism test is required before administration of the antiretroviral drug maraviroc. However, plasma RNA testing is not possible in patients with undetectable plasma viral loads. Here we assess genotypic testing of cellular human immunodeficiency virus (HIV) DNA from peripheral blood mononuclear cells (PBMCs) to predict virologic responses in treatment-experienced patients beginning maraviroc-containing regimens.
  
  
  METHODS
  PBMC samples from 181 maraviroc recipients at study entry in MOTIVATE or A4001029 (51% R5 by original Trofile). The V3 loop was amplified in triplicate from cellular HIV DNA, and matching plasma RNA (n = 156). Sequencing was performed using standard population-based methods and next-generation deep sequencing, with tropism assessment as previously defined.
  
  
  RESULTS
  Genotypic DNA-based tropism testing from the cellular compartment had 78%-81% sensitivity relative to RNA-based Trofile at the same time point. Cell-based genotypic tropism methods and plasma-based phenotypic and genotypic methods were predictive of virologic response. However, when classifications were discordant, the outcomes favored the plasma predictions over the DNA ones.
  
  
  CONCLUSIONS
  Genotypic determination of HIV tropism can be performed using cell-derived viral DNA, and is a predictor of virologic success on maraviroc in therapy-experienced patients. However, the PBMC compartment appears to be a suboptimal predictor compared to plasma.
authors: BC Centre for Excellence in HIV/AIDS, Vancouver, Canada.
authors: Luke C
authors: LC
authors: Swenson
authors: Winnie W Y
authors: WW
authors: Dong
authors: Theresa
authors: T
authors: Mo
authors: James
authors: J
authors: Demarest
authors: Doug
authors: D
authors: Chapman
authors: Suzanne
authors: S
authors: Ellery
authors: Jayvant
authors: J
authors: Heera
authors: Hernan
authors: H
authors: Valdez
authors: Art F Y
authors: AF
authors: Poon
authors: P Richard
authors: PR
authors: Harrigan
mesh_terms: D003510:Cyclohexanes / Q000494:pharmacology* / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood*; D005838:Genotype; D006678:HIV / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D023581:HIV Fusion Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D007963:Leukocytes, Mononuclear / Q000821:virology; D000077592:Maraviroc; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D056189:Viral Tropism / Q000235:genetics
chemical_list: D003510:Cyclohexanes; D004279:DNA, Viral; D023581:HIV Fusion Inhibitors; D014230:Triazoles; D000077592:Maraviroc
keywords: HIV coreceptor-usage/tropism; HIV proviral DNA; maraviroc; next-generation sequencing