CD4 + T-cell depletion in the gut occurs inexorably and rapidly after HIV infection,160 regardless of the route of exposure, and long before CD4 + T-cell reductions occur in blood or lymph nodes.161 Th1, Th17, and Th22 cells, which are specific subsets of CD4 + T-cells, critically important (i) for initiation of primary immune responses and (ii) for maintenance of mucosal integrity, are selectively targeted and eliminated first 160 (Figure 3). This evidence concerns the gene CD4 and HIV infectious disease.