The long terminal repeat (LTR) region of HIV-1 promotes and modulates proviral transcription. LTR genetic variability might influence viral replication and disease progression. Proviral LTR sequences from 32 HIV-1-infected individuals showing different rates of disease progression were examined. Non-progressors (NP, n = 11) were individuals with high and stable CD4 counts and persistently low or undetectable plasma HIV-RNA. Slow progressors (SP, n = 6) were subjects with minimal CD4 decays over time and low plasma HIV-RNA. Typical progressors (TP, n = 15) were individuals with chronic infection showing CD4 counts repeatedly below 500 cells/mul. The mutation frequency within distinct LTR functional regions involved in HIV-1 transcription were compared in these three groups of patients. No significant differences were observed in the mutation frequency in most LTR regulatory sites when comparing the three groups. However, changes in USF regulatory binding sites were more frequent in TP than in SP/NP, while changes in Sp1 binding sites were less common in the former. This is the first study examining the genetic variability of the HIV-1 LTR region in long-term non-progressors showing further divergent outcomes.