To analyse sociodemographic, viroimmunological and clinical parameters in different HIV-transmission categories at baseline and during treatment, 3039 patients were followed up for 12 months after the initiation of a nelfinavir-based regimen. Multiple baseline parameters were significantly different in the diverse categories, including CD4 counts (P<0·0001) and viral load (P=0·02). There were differences in the groups regarding the CD4 response (P=0·01), but not the virological response (P=0·4), to therapy over time. Multivariate analyses revealed that transmission categories were significantly related to baseline CD4 counts (P=0·01), viral load at 12 months (P=0·0006), poorer adherence to therapy of injecting drug users (IDUs) vs. each of the other groups (P<0·001) and failure to complete the 12-month evaluation of IDU vs. heterosexual (P=0·003) and men who have sex with men (MSM) groups (P=0·02). We conclude that transmission categories had a significant influence on several baseline parameters and viroimmunological outcomes following highly active antiretroviral therapy (HAART), as well as on adherence to therapy and to medical appointments.