Although potential mechanisms for Ad5 vector-associated excess HIV infections in the Step and Phambili studies are thought to be complex and could be affected by different factors such as the quantity, quality and in vivo localization of CD4 T cells induced during vaccination, our findings suggest that understanding the HIV susceptibility of vector-specific CD4 T-cell populations induced by different vaccine vectors may provide new insights into our understanding of host immunity in HIV vaccination. This evidence concerns the gene CD4 and HIV infectious disease.