title: Trends and correlates of HIV-1 resistance among subjects failing an antiretroviral treatment over the 2003-2012 decade in Italy.
abstract: BACKGROUND
  Despite a substantial reduction in virological failures following introduction of new potent antiretroviral therapies in the latest years, drug resistance remains a limitation for the control of HIV-1 infection. We evaluated trends and correlates of resistance in treatment failing patients in a comprehensive database over a time period of relevant changes in prescription attitudes and treatment guidelines.
  
  
  METHODS
  We analyzed 6,796 HIV-1 pol sequences from 49 centres stored in the Italian ARCA database during the 2003-2012 period. Patients (n = 5,246) with viremia > 200 copies/mL received a genotypic test while on treatment. Mutations were identified from IAS-USA 2013 tables. Class resistance was evaluated according to antiretroviral regimens in use at failure. Time trends and correlates of resistance were analyzed by Cochran-Armitage test and logistic regression models.
  
  
  RESULTS
  The use of NRTI backbone regimens slightly decreased from 99.7% in 2003-2004 to 97.4% in 2010-2012. NNRTI-based combinations dropped from 46.7% to 24.1%. PI-containing regimens rose from 56.6% to 81.7%, with an increase of boosted PI from 36.5% to 68.9% overtime. In the same reference periods, Resistance to NRTIs, NNRTIs and PIs declined from 79.1% to 40.8%, from 77.8% to 53.8% and from 59.8% to 18.9%, respectively (p < .0001 for all comparisons). Dual NRTI + NNRTI and NRTI + PI resistance decreased from 56.4% to 33.3% and from 36.1% to 10.5%, respectively. Reduced risk of resistance over time periods was confirmed by a multivariate analysis.
  
  
  CONCLUSIONS
  Mutations associated with NRTIs, NNRTIs and PIs at treatment failure declined overtime regardless of specific class combinations and epidemiological characteristics of treated population. This is likely due to the improvement of HIV treatment, including both last generation drug combinations and prescription guidelines.
authors.affiliation: Department of Biomedical and Clinical Sciences 'L, Sacco', Infectious Diseases and Immunopathology Section, University of Milan, Milan, Italy. marco.franzetti@guest.unimi.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Franzetti
authors.forename: Michela
authors.initials: M
authors.lastname: Violin
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zazzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Balotta
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000145:classification / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors