title: Comparison of a rule-based algorithm with a phenotype-based algorithm for the interpretation of HIV genotypes in guiding salvage regimens in HIV-infected patients by a randomized clinical trial: the mutations and salvage study.
abstract: BACKGROUND
  There is still considerable uncertainty as to the best algorithm for interpreting human immunodeficiency virus (HIV) genotyping results.
  
  
  METHODS
  A total of 318 subjects with HIV RNA levels of >1000 copies/mL were enrolled in 41 centers throughout Italy from 2001 through 2003, stratified on the basis of their drug history, randomized (1:1) to 2 arms to have their treatments modified on the basis of the results of HIV genotyping (as interpreted by virtual phenotype analysis or with use of a rule-based interpretation system), and followed up for 48 weeks. At least 1 nucleoside reverse-transcriptase inhibitor and 1 protease inhibitor had to be included in any new regimen; nonnucleoside reverse-transcriptase inhibitor-naive patients were also prescribed a nonnucleoside reverse-transcriptase inhibitor. Only drugs licensed in Italy were allowed. The primary end point was a decrease in HIV RNA level to <400 copies/mL by week 12 according to on-treatment analysis.
  
  
  RESULTS
  The mean (+/- standard deviation) values at baseline were as follows: HIV RNA level, 4.1+/-0.74 log(10) copies/mL; CD4(+) T lymphocyte count, 410+/-262 cells/microL; reverse-transcriptase mutations, 4.8+/-2.9; and protease mutations, 2.8+/-2.5. There were 133 patients (41.8%) who were nonnucleoside reverse-transcriptase inhibitor naive and protease inhibitor experienced, 63 patients (19.8%) who were nonnucleoside reverse-transcriptase inhibitor experienced and protease inhibitor naive, and 122 patients (38.4%) who were 3-class experienced. A total of 192 patients completed 12 weeks of the treatment regimen assigned at baseline; at 12 weeks, 66.3% of patients in the virtual phenotype arm and 71.3% of patients in the rule-based interpretation arm had HIV RNA levels of <400 copies/mL (P = .46). No statistically significant difference between arms was observed by intention-to-treat analysis.
  
  
  CONCLUSIONS
  Both the virtual phenotype and rule-based interpretation methods of HIV genotyping can guide the selection of effective antiretroviral drugs for a salvage regimen.
authors.affiliation: Clinica di Malattie Infettive, Università Vita-Salute San Raffaele, Milan, Italy. nicola.gianotti@hsr.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mondino
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Rossi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Chiesa
authors.forename: Ivano
authors.initials: I
authors.lastname: Mezzaroma
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tarquini
authors.forename: Paula
authors.initials: P
authors.lastname: Castelli
authors.forename: Aldo
authors.initials: A
authors.lastname: Di Carlo
authors.forename: Enzo
authors.initials: E
authors.lastname: Boeri
authors.forename: Wilco
authors.initials: W
authors.lastname: Keulen
authors.forename: Paula Mc
authors.initials: PM
authors.lastname: Kenna
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
mesh_terms: D000328:Adult; D000465:Algorithms; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D005838:Genotype; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016879:Salvage Therapy; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors