CD4 and HIV infectious disease: In the acute phase of HIV infection, the direct impact of viral replication has been shown to significantly contribute to the initial loss of CD4+ T cells via: (i) the increased permeability of the cell membrane after viral budding and/or syncytium formation resulting in cytolysis, (ii) the induction of HIV-specific CD8+ cytotoxic T lymphocytes, which target and eliminate virally infected cells, and (iii) the programmed cell death of cells undergoing productive infection due to caspase-3 and/or Bax activation [11].