To evaluate the impact of injection drug users (IDUs) adherence on effectiveness of highly active antiretroviral therapy (HAART), repeated measures of plasma viral load and CD4+ counts before HAART initiation and at last visit in the cohort were studied. Data were collected by means of patient's face-to-face and self-administered questionnaires about adherence to HAART during the week prior to the last visit. Of a total of 119 patients treated with HAART, undetectable viral load was obtained for 55 patients (46.2%) (G3); 34 patients (28.6%) (G2) had a viral load decline > 0.5 log copies/ml but still detectable viral load at last visit in the cohort, while 30 patients (25.2%) (G1) had no decline or decline </= 0.5 log copies/ml. Proportion of 100% adherent patients was significantly higher in G3 (83.6%) than in G2 (64.7%) and G1 (56.7%). In spite of differences in virological success and adherence, mean increase in CD4+ counts was similar in G3 (123 +/- 160 counts/mm(3)) and G2 (143 +/- 147) while no immunological improvement was observed in G1. For the sub-groups of patients whose limited adherence has implied virological failure but did not impede short-term immunological reconstitution following HAART initiation, decision to switch HAART regimens could be delayed until interventions for improving future adherence have been carried out.