title: Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy.
abstract: OBJECTIVE
  Maraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment.
  
  
  METHODS
  HIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated.
  
  
  RESULTS
  Coreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing.
  
  
  CONCLUSIONS
  HIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option.
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Genny
authors.initials: G
authors.lastname: Meini
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossetti
authors.forename: Claudia
authors.initials: C
authors.lastname: Bianco
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.forename: Laura
authors.initials: L
authors.lastname: Sighinolfi
authors.forename: Laura
authors.initials: L
authors.lastname: Monno
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.forename: Gabriella
authors.initials: G
authors.lastname: Rozera
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Arminio Monforte
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zazzi
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000235:genetics*; D017422:Sequence Analysis, DNA; D056189:Viral Tropism
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral
keywords: HIV type 1; V3; genotype interpretation; gp120