Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naive patients.

OBJECTIVES: 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 antiretrovial therapy (HAART) in an Italian cohort. METHODS: We included in the study patients from the Italian Cohort Naive Antiretrovirals (ICoNA) who initiated HAART when naive to antiretroviral therapy (ART). The endopoints were discontinuation within the first year of >or=1 drug in the first HAART regimen for nay 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 discontiuation 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 ther 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.