Major differences exist between HIV-1 and HIV-2 in terms of epidemiology, pathogenicity, sensitivity to antiretrovirals. Determining the type of HIV infecting a patient is essential for management. The aim of this study was to evaluate the ability of simple/rapid tests to differentiate between HIV-1 and/or HIV-2 infections. We analyzed 116 samples from patients infected with HIV-1 (n = 61), HIV-2 (n = 47), or HIV-1+HIV-2 (n = 8) at the chronic stage of infection. Each sample was tested with SD Bioline HIV-1/2 3.0, ImmunoFlow HIV1–HIV2, ImmunoFlow HIV1–HIV2 (WB), Genie III HIV-1/HIV-2, ImmunoComb HIV1&2 BiSpot. HIV-1, or HIV-2 single infection was identified with a sensitivity ranging from 90% to 100%. The ability to detect dual infection was less sensitive (12.5–100%). SD Bioline HIV-1/2 3.0, ImmunoFlow HIV1–HIV2, and Genie III were unable to detect HIV-1 group O infection in one, one and two cases, respectively. The specificity of detection of HIV-1, HIV-2, or HIV-1+HIV-2 antibodies differed greatly (36–100%). ImmunoComb BiSpot had the highest sensitivity values (99–100% for HIV-1, 98% for HIV-2, and 75–87.5% for dual infection) and specificity values (94–100% for HIV-1, 100% for HIV-2, and 97–100% for dual infection). In conclusion, this study showed that no single rapid test had a perfect sensitivity/specificity ratio, particularly in the case of the double infections. J. Med. Virol. 87:2061–2066, 2015. © 2015 Wiley Periodicals, Inc.