We assessed predictors of discontinuation or change of the first regimen of highly active antiretroviral therapy in 465 HIV-infected adults, in the first year. A total of 187 patients modified their regimen: 45 discontinuing and 142 changing because of clinical/virological failure, intolerance/toxicity or non-adherence. Predictors of modification of the regimen were hepatitis C seropositivity, liver cirrhosis, higher baseline viral load, sex (women had a lower risk) and calendar year (lower risk staring in 2000).