Furthermore, another relevant observation is that strong anti-MPER responses occur in patients with strong anti-Envelope responses, suggesting that no specific requirements are needed for such a responses, and that the general immunocompetence, defined by the suboptimal function of CD4 and B cell compartments [28], may be the main limiting factor in the elicitation of strong humoral responses in natural HIV-1 infection. This evidence concerns the gene CD4 and HIV-1 infection.