title: Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naïve patients.
abstract: OBJECTIVE
  The aim of the study was to determine whether the incidence of first-line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort.
  
  
  METHODS
  We included in the study patients from the Italian COhort Naïve Antiretrovirals (ICoNA) who initiated HAART when naïve to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of >or= 1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as 'early', 1997-1999; 'intermediate', 2000-2002; 'recent', 2003-2007) was associated with the probability of reaching the endpoints by a survival analysis.
  
  
  RESULTS
  Overall, the 1-year probability of discontinuation of >or= 1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all-reason change were comparable according to calendar period [2000-2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0.69-0.98; 2003-2007, ARH 0.94, 95% CI 0.76-1.16, vs. 1997-1999; global P-value = 0.08]. Patients who started HAART during the 'recent' period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51-0.89 vs. 'early' period). Patients who started in the 'intermediate' and 'recent' periods had a higher risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21-72.45, and ARH 37.97, 95% CI 7.56-190.64, vs. 'early' period, respectively).
  
  
  CONCLUSIONS
  It seems important to evaluate reason-specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation.
authors.affiliation: Department of Infectious Diseases and Tropical Medicine, Università degli Strudi di Milano H. S. Paolo, Milan, Italy. paola.cicconi@unimi.it
authors.forename: Paola
authors.initials: P
authors.lastname: Cicconi
authors.forename: A
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: A
authors.initials: A
authors.lastname: Castagna
authors.forename: E M
authors.initials: EM
authors.lastname: Trecarichi
authors.forename: A
authors.initials: A
authors.lastname: Antinori
authors.forename: F
authors.initials: F
authors.lastname: Gatti
authors.forename: G
authors.initials: G
authors.lastname: Cassola
authors.forename: L
authors.initials: L
authors.lastname: Sighinolfi
authors.forename: P
authors.initials: P
authors.lastname: Castelli
authors.forename: A
authors.initials: A
authors.lastname: d'Arminio Monforte
mesh_terms: D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000706:statistics & numerical data*; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011247:Pregnancy; D012737:Sex Factors; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents