We assessed HIV-1 and HIV-2 2-long terminal repeat (LTR) circular DNA production in peripheral blood mononuclear cells, MT4-CXCR4 cells and HeLa-CXCR4-CCR5 cells in vitro, relative to the respective total amounts of HIV DNA. Whatever the cell type, HIV-2 produced a smaller total amount of DNA than HIV-1 between 6 and 96 h; HIV-2 2-LTR DNA appeared later than HIV-1 2-LTR DNA, but rapidly became more abundant. This accumulation of HIV-2 2-LTR DNA points to less efficient host cell integration relative to HIV-1.