title: Deep V3 sequencing for HIV type 1 tropism in treatment-naive patients: a reanalysis of the MERIT trial of maraviroc.
abstract: BACKGROUND
  Deep sequencing is a highly sensitive technique that can detect and quantify the proportion of non-R5 human immunodeficiency virus (HIV) variants, including small minorities, that may emerge and cause virologic failure in patients who receive maraviroc-containing regimens. We retrospectively tested the ability of deep sequencing to predict response to a maraviroc-containing regimen in the Maraviroc versus Efavirenz in Treatment-Naive Patients (MERIT) trial. Results were compared with those obtained using the Enhanced Sensitivity Trofile Assay (ESTA), which is widely used in clinical practice.
  
  
  METHODS
  Screening plasma samples from treatment-naive patients who received maraviroc and efavirenz in the MERIT trial were assessed. Samples were extracted, and the V3 region of HIV type 1 glycoprotein 120 was amplified in triplicate and combined in equal quantities before sequencing on a Roche/454 Genome Sequencer-FLX (n = 859). Tropism was inferred from third variable (V3) sequences, with samples classified as non-R5 if ≥2% of the viral population scored ≤3.5 using geno2pheno.
  
  
  RESULTS
  Deep sequencing distinguished between responders and nonresponders to maraviroc. Among patients identified as having R5-HIV by deep sequencing, 67% of maraviroc recipients and 69% of efavirenz recipients had a plasma viral load <50 copies/mL at week 48, similar to the ESTA results: 68% and 68%, respectively.
  
  
  CONCLUSIONS
  Reanalysis of the MERIT trial using deep V3 loop sequencing indicates that, had patients originally been screened using this method, the maraviroc arm would have likely been found to be noninferior to the efavirenz arm.
authors: BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
authors: Luke C
authors: LC
authors: Swenson
authors: Theresa
authors: T
authors: Mo
authors: Winnie W Y
authors: WW
authors: Dong
authors: Xiaoyin
authors: X
authors: Zhong
authors: Conan K
authors: CK
authors: Woods
authors: Alexander
authors: A
authors: Thielen
authors: Mark A
authors: MA
authors: Jensen
authors: David J H F
authors: DJ
authors: Knapp
authors: Douglass
authors: D
authors: Chapman
authors: Simon
authors: S
authors: Portsmouth
authors: Marilyn
authors: M
authors: Lewis
authors: Ian
authors: I
authors: James
authors: Jayvant
authors: J
authors: Heera
authors: Hernan
authors: H
authors: Valdez
authors: P Richard
authors: PR
authors: Harrigan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D048588:Benzoxazines / Q000008:administration & dosage; D003510:Cyclohexanes / Q000008:administration & dosage; D003521:Cyclopropanes; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage; D056189:Viral Tropism; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003510:Cyclohexanes; D003521:Cyclopropanes; D015699:HIV Envelope Protein gp120; D014230:Triazoles; C514793:gp120 protein, Human immunodeficiency virus 1; C098320:efavirenz; D000077592:Maraviroc