title: Prevalence of R5 strains in multi-treated HIV subjects and impact of new regimens including maraviroc in a selected group of patients with CCR5-tropic HIV-1 infection.
abstract: OBJECTIVE
  Maraviroc currently represents an important antiretroviral drug for multi-experienced and viremic HIV patients. This study focused on two main points: (1) determining the prevalence of R5 and X4 HIV strains in antiretroviral-experienced patients using two main tests currently in use to determine viral tropism, and (2) the follow-up to 3 years of a limited number of patients who started a new antiretroviral protocol including maraviroc.
  
  
  METHODS
  A group of 56 HIV patients, previously multi-treated, were first analyzed by genotyping assay and Trofile™ to establish their eligibility for maraviroc treatment. In addition, 25 subjects selected to follow a new therapeutic protocol including a CCR5 antagonist were monitored by HIV RNA viral load and CD4+ cell count.
  
  
  RESULTS
  The determination of viral tropism showed a large percentage of patients with an R5 profile (72% by genotyping assay and 74% by Trofile). The follow-up of most (21 out 25) patients who started the new antiretroviral protocol showed an undetectable viral load throughout the observation period, accompanied by a major improvement in CD4 cell count (cells/mm(3)) (baseline: median CD4 cell count 365, interquartile range (IQR) 204-511; 12 months: median value 501, IQR 349-677, p=0.042; 24 months: median value 503, IQR 386-678, p=0.026; 36 months: median value 601, IQR 517-717, p=0.001). Among the four non-responder subjects, two showed a lack of drug compliance and two switched from R5 to X4.
  
  
  CONCLUSIONS
  Although our patient cohort was small, the results showed a high prevalence of R5 viral strains in multi-experienced patients. As well as showing the advantages of genotyping, which can be performed in plasma samples with low viral load replication, the follow-up of HIV patients selected for an alternative drug protocol, including a CCR5 antagonist, showed a persistent undetectable viral replication and a good recovery of CD4 cell count in most treated HIV patients.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Bon
authors.forename: Alberto
authors.initials: A
authors.lastname: Clò
authors.forename: Marco
authors.initials: M
authors.lastname: Borderi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Colangeli
authors.forename: Leonardo
authors.initials: L
authors.lastname: Calza
authors.forename: Silvia
authors.initials: S
authors.lastname: Morini
authors.forename: Anna
authors.initials: A
authors.lastname: Miserocchi
authors.forename: Monica
authors.initials: M
authors.lastname: Cricca
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Re
mesh_terms: D000328:Adult; D000368:Aged; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D057915:Drug Substitution; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D023581:HIV Fusion Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D015995:Prevalence; D019713:Receptors, CCR5 / Q000502:physiology*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects; D056189:Viral Tropism; D014779:Virus Replication; D055815:Young Adult
chemical_list: D065100:CCR5 Receptor Antagonists; C584933:CCR5 protein, human; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc
keywords: Genotyping test; HIV; Maraviroc; Trofile™; Tropism