In 29 antiretroviral-naive HIV-2-infected patients starting lopinavir/ritonavir-containing regimen, the median CD4 cell count change from baseline (142 cells/microl) was +71 cells/microl at week 24 and +132 cells/microl at week 96. Seventeen (59%) patients had a CD4 cell count increase of at least 50 cells/microl and undetectable HIV-2 RNA at week 24 and were considered as responders to treatment. This sustained elevation of CD4 cell count in the first 2 years of combination antiretroviral therapy shows the potential for lopinavir/ritonavir regimens as first-line therapy in HIV-2 infection.