WHAT IS KNOWN AND OBJECTIVE: The trajectory of HIV viral load and CD4 count and the occurrence of clinical events are primary considerations in the evaluation of antiretroviral therapy (ART) success or failure, yet a large number of studies do not describe these events from the point of therapy initiation. This study aims to describe the virological and immune response to ART and factors associated with immune and virological success in outpatients from a HIV/AIDS clinic in southern Brazil from therapy initiation. METHODS: Longitudinal observational with ambidirectional data collection study with adult patients followed for at least 12 months after enrolment. Outcomes include (i) favourable immune response, defined as CD4 count ≥200 cells/mm³; and (ii) virological success, defined as viral load below the limit of detection (50 copies/mL). RESULTS: The study included 332 patients, mostly men (63%), whose mean age was 40 (±10) years and with median family income of BR$ 490·00 per month (IQR: 350-875). Before starting ART, 43% of patients had indications of stable immune status (CD4 count ≥200 cells/mm³); the median CD4 count was 179 cells/mm³ (IQR: 93·5, 267) and increased to 379·5 cells/mm³ (IQR: 236·5, 591·3). The proportion of patients with CD4 count ≥200 cells/mm³ increased from 76% to 83%, and with undetectable viral load (UVL) increased from 51·7% to 73%. Factors associated with immune success at the end of study follow-up were as follows: female gender, pretreatment CD4 count ≥200 cells/mm³, previous UVL (measured when started prospective follow-up) and treatment with three drugs compared with ≥4. Factors associated with virological success were as follows: UVL (measured when started prospective follow-up) and use of three drugs compared with ≥4. WHAT IS NEW AND CONCLUSIONS: Results of this study show that a large proportion (73%) of patients have rapid and successful immune and virological responses to ART and that factors which predict this response include starting ART early, whereas viral load is low and CD4 count is high, with fewer drugs. These results further support the ongoing need for ongoing programmes to increase early HIV testing, early linkage to and treatment with ART, and increased viral suppression.