Using an optimized HIV co-culture protocol it was possible to isolate infectious HIV-2 variants from 6 HIV-2-infected individuals who had undetectable plasma viremia and maintained high CD4+ T-cell numbers for prolonged periods. This shows for the first time that HIV-2-infected individuals with no demonstrable in vivo virus production carry replication-competent virus in peripheral blood mononuclear cells (PBMCs). The frequency of PBMCs with infectious virus was low, ranging from 0.01–0.9 infectious units per million (IUPM) CD4+ T cells with a median value of 0.2 IUPM. In comparison, viremic HIV-2-infected individuals had a 2-log higher median infectious load (36 IUPM, range 1–673; P = 0.003). HIV-2 infectious load correlated with CD4 counts (rs = −0.88, P < 0.0001). The low infectious load in aviremic HIV-2-infected persons is reminiscent of what has been observed for HIV-1 infection controlled by highly active antiretroviral therapy.