To further define important mutations in HSIV-vif that confer increased viral fitness in PTMs, we isolated and characterized variant virus isolates from peripheral blood CD4+ T cells after 196–200wpi with HSIV-vifNL4-3 infection when there was CD4+ T cell depletion, and then performed a serial in vivo passaging experiment using a mixture of these virus isolates and different clones of HSIV-vif to define genetic characteristics that could contribute to persistent viral replication in vivo. This evidence concerns the gene CD4 and infection.