CD4 and infection: It has been reported that CD4+T-cell loss may be attributed to one of the following: (i) direct destruction by HIV cytopathic effects [33]; (ii) apoptosis induced by HIV proteins, such as Env, Tat (Tatanus antitoxin), Nef, Vpu and Vpr, which were proposed by Gougeon et al. in the 1990s [19,20] and reviewed by Gougeon [18]; (iii) excessive infection-induced immune cells activation drives CD4+T-cell depletion [14]; (iv) HIV-1-induced apoptosis in bystander uninfected cells [1].