HAND diagnosis is not straightforward due to the existence of other clinical factors associated with HIV-1 infection [4,72,73] such as virus subtypes (clades) [74], high viral load, and low CD4 counts [75], HAND-associated risk factors [76,77], long-term exposure to cART [78], comorbidities [31,79,80], sociocultural/ethnic backgrounds [15,16,17,64] and genetic factors [81,82]. Here, CD4 is linked to HIV-1 infection.