CD4 and infection: The massive HIV-1 replication that takes place in the gastrointestinal tract early in the course of the infection not only plays a critical role in the massive depletion of CD4+ T cells within the lamina propria, but also results in a seemingly irreversible damage to the architecture of the intestinal mucosa leading to crypt hyperplasia, decreased number of Paneth cells and decreased levels of luminal defensins [59], [60].