title: Response to antiretroviral treatment after failure of NNRTI plus NRTIs-based therapy. Data from the ARCA collaborative group.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the virological response to a new antiretroviral treatment (ART2) after failure of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs)-containing regimen.
  
  
  METHODS
  Retrospective observational study based on the Italian ARCA cohort database. Adult patients were included if they had a virological failure (defined as plasma viral load above 500 copies/ml in two subsequent visits) while on a treatment with one NNRTI plus 2 NRTIs, had an available HIV genotype.
  
  
  RESULTS
  Patients on ART2 were followed up for 791 person/year and median follow up was 10.8 months(IQR 5.2-26). Variables associated with reduced risk of ART2 virological failure at univariable analysis had started the treatment in recent years (HR 0.90; 95% CI 0.86-0.94, p < 0.0001) and duration of previous NNRTI treatment (HR 0.995; 95%CI 0.990-0.990, p=0.045). Variables associated with increased risk of virological failure of ART2 were a higher plasma viral load (pVL) at baseline(HR 1.2; 95% CI 1.07-1.34, p=0.002) and the type of treatment, in particular an unboosted PI-containing regimen vs. a boosted PI-containing regimen(HR 1.6; 95%CI 1.25-2.04 p < 0.0001) and a non-PI-containing vs. a boosted PI-containing regimen (HR 1.56; 95% CI 1.25-1.96, p < 0.0001). At multivariable analysis, year of ART2 start, pVL at NNRTI failure as well as using a boosted PI remained statistically significant predictors.
  
  
  CONCLUSIONS
  This study highlights the role of drugs with high genetic barrier, such as boosted PI as a cornerstone to build a new antiretroviral treatment in patients failing a NNRTI based regimen.
authors.affiliation: Clinica di Malattie Infettive e Tropicali, Ospedale di Circolo-Fondazione Macchi, Varese, Italy. elenaseminari@yahoo.com
authors.forename: Elena
authors.initials: E
authors.lastname: Seminari
authors.forename: Annalisa
authors.initials: A
authors.lastname: De Silvestri
authors.forename: Genny
authors.initials: G
authors.lastname: Meini
authors.forename: Annapaola
authors.initials: A
authors.lastname: Callegaro
authors.forename: Enzo
authors.initials: E
authors.lastname: Boeri
authors.forename: Grazia
authors.initials: G
authors.lastname: Punzi
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.forename: Bianca
authors.initials: B
authors.lastname: Bruzzone
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Grossi
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D054303:HIV Reverse Transcriptase