title: Phenotype or virtual phenotype for choosing antiretroviral therapy after failure: a prospective, randomized study.
abstract: BACKGROUND
  Resistance testing is useful in the management of virological failure patients, although the best method to be used in clinical practice has not been determined.
  
  
  METHODS
  A prospective, randomized, double-blind, multicentre, controlled clinical trial was performed to compare the usefulness of drug resistance testing with a recombinant viral phenotype method or with a virtual phenotype, a genotyping interpretation system. Planned 300 HIV-infected adults failing their current antiretroviral therapy (HIV RNA > 1000 copies/ml) were centrally randomized 1:1 to resistance testing with a recombinant viral phenotype method or with a virtual phenotype, after stratifying according to previous drug exposure (one or two versus three drug classes). Percent of patients with HIV RNA suppression (% < 400 copies/ml) after 24 weeks was the primary outcome variable. Median HIV RNA concentration and change from baseline in HIV RNA concentration were also used to compare effectiveness. An extended analysis was performed at week 48.
  
  
  RESULTS
  Of the 300 patients enrolled, a total of 276 patients could be analysed; 139 patients were randomized to the phenotype group and 137 patients were randomized to the virtual phenotype group. After 24 weeks of follow-up, 46.8 and 56.2% of patients had HIV RNA < 400 copies/ml (P = 0.1) in the phenotype and virtual phenotype, respectively. Mean decrease from baseline in viral load was 1.0 and 1.3 log copies/ml in the phenotype and virtual phenotype groups, respectively (P = 0.017). In a multivariate linear regression analysis, after adjusting for baseline HIV RNA and adherence to treatment, the virtual phenotype was associated with a greater mean decrease in plasma HIV RNA (P = 0.0063). The results observed at week 48 were similar.
  
  
  CONCLUSIONS
  Virtual phenotype is at least as effective as phenotype when used to select an optimized treatment for patients who have failed one or more antiretroviral regimens.
authors.affiliation: Infectious Diseases Service, Clinical Research Department, Ramón y Cajal Hospital, Madrid, Spain. mjperez@telefonica.net
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Perez-Elias
authors.forename: Isabel
authors.initials: I
authors.lastname: Garcia-Arota
authors.forename: Vicente
authors.initials: V
authors.lastname: Muñoz
authors.forename: Ignacio
authors.initials: I
authors.lastname: Santos
authors.forename: José
authors.initials: J
authors.lastname: Sanz
authors.forename: Victor
authors.initials: V
authors.lastname: Abraira
authors.forename: José R
authors.initials: JR
authors.lastname: Arribas
authors.forename: Juan
authors.initials: J
authors.lastname: González
authors.forename: Ana
authors.initials: A
authors.lastname: Moreno
authors.forename: Fernando
authors.initials: F
authors.lastname: Dronda
authors.forename: Antonio
authors.initials: A
authors.lastname: Antela
authors.forename: María
authors.initials: M
authors.lastname: Pumares
authors.forename: Paloma
authors.initials: P
authors.lastname: Martí-Belda
authors.forename: Jose L
authors.initials: JL
authors.lastname: Casado
authors.forename: Paloma
authors.initials: P
authors.lastname: Geijos
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006678:HIV / Q000145:classification / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents