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To characterize the subtype C strains of HIV type 1 that circulate in Brazil, especially those originated from the southern part of the country.One hundred and twelve HIV-1-positive subjects had their plasma viral RNA extracted. Protease (PR) and reverse transcriptase (RT) genomic regions were polymerase chain reaction-amplified and sequenced for subtype determination. Subtype C strains were selected and compared to other strains of this subtype from the database, and specific amino acid signature patterns were searched.Brazilian subtype C viruses form a very strong monophyletic group when compared to subtype C viruses from other countries and presented specific signature amino acids. Recombinants between subtype C and B viruses have been documented in areas of co-circulation. The incidence of primary PR and RT inhibitor resistance mutations in drug-naïve subjects was observed. An increasing number of secondary resistance mutations was also seen, some of which are characteristic of subtype C-related sequences.Introduction of subtype C of HIV-1 in Brazil was likely a single event of one or a mixture of similarly related strains. Recombination between subtype C and B viruses is an ongoing process in the country. Primary and secondary drug resistance mutations were observed, although some of the secondary mutations could be associated with subtype C molecular signatures. Subtype-specific polymorphisms of PR and RT sequences found in this subtype C Brazilian variant might influence this emergence and have an impact on HIV treatment and on vaccine development in the country.