Among the 3700 HIV-infected patients followed in our institution, 17 with regular clinical, immunological and virological follow-up and identified as being dually seropositive for HIV-1 and HIV-2 were included in this study. Antiretroviral therapy seemed to be as effective, in terms of virological and immunological response, as in patients infected by HIV-1 alone. Nevertheless, the observed selection of HIV-2 protease resistance mutations in two cases underlines the importance of selecting drugs that are active on both viruses.