Objectives: We evaluated the HIV-1 subtype diversity, clinical, genetic and epidemiological profiles of a cohort of long-term non-progressor (LTNPs) followed-up at a referral hospital in southern Brazil. Methods: This prospective study included patients who had more than eight years of HIV-1 diagnosis without antiretroviral therapy (ART). Clinical and epidemiological profiles of LTNPs were obtained from interviews and medical records. Periodic blood draws were taken to determine HIV-1 genetic variability and host genetic patterns. Results: The study included 22 LTNPs, corresponding to 1.57% of patients followed-up at the Infectious Diseases Division. The gender distribution was nearly homogeneous, median age was 45 years; 18% were elite controllers, 23% were viremic controllers and 59% were non-viremic controllers. Three out of 22 patients were heterozygous for the CCR5Δ32 genotype. In most study patients, receptor use was consistent with an R5 phenotype. HIV-1 genotyping showed subtype C in 50% (11/22) of patients, subtype B in 32% (7/22), and the recombinant forms BF and BC in 14% (3/22) and 4% (1/22), respectively. There was a significant association of subtype C with female patients, and LTNPs patients infected with subtype C had lower viral loads compared with those infected with subtype B. Conclusions: The HIV/AIDS epidemic in Brazil is complex, and there are variations in the subtype distribution. This is the first study of LTNPs in the southern region of Brazil, and the data obtained will help to characterize this group and aid in determining the probable mechanisms associated with delayed clinical progression.