In conclusion, our findings show that MΦ-tropism of primary HIV-1 isolates, currently based on cell-free infection assays, needs to be revisited to reflect the capacity of both CCR5- and CXCR4-using non-M-tropic variants, including some T/F viruses, to spread efficiently in myeloid cells via cell-to-cell transfer from infected T cells. This evidence concerns the gene CXCR4 and infection.