A low CD4+ T-cell count at the start of cART has been associated with clinical progression [2, 7] and hampered immune-reconstitution (reviewed in [8]; [9, 10]); of note, a low CD4+ T-cell nadir has also been shown to mirror the complex alterations of peripheral T-cell homeostasis in HIV infection, ranging from the impairment of lymphocyte maturation and function to increases in T-cell activation, death and T-regulatory cell (Treg) activity, which may not be reverted by treatment [9–20]. Here, CD4 is linked to HIV infectious disease.