Key points 堃linical diagnosis of HIV infection requires consideration of HIV aetiology in relation to a range of sub-acute, chronic and acute clinical presentations. 堃hronic symptoms of immune activation (e.g. lymphadenopathy, night sweats, fever) may indicate HIV infection. 堍ild, HIV-related immune deficiency may be indicated by persistent oral or skin conditions. 堌aboratory markers such as thrombocytopenia, neutropenia and lymphopenia may suggest HIV infection. 堔he incidence of 'classical' AIDS-defining illnesses has fallen dramatically in Australia since the introduction of combination antiretroviral therapy. These conditions are now most common among patients with advanced HIV disease whose HIV status has been undiagnosed. 堃ombination antiretroviral therapy has dramatically altered the course of clinical HIV disease. Immune reconstitution illness and treatmentrelated side-effects are now common causes of clinical symptoms.