The risk factors and comorbidities for HAND and implicitly HAD and/or non-HIV-related cognitive impairment include disease factors (i.e., low nadir CD4 cell count, high plasma or CSF HIV RNA, low current CD4, history of HIV-related CNS diseases, longer HIV duration), treatment factors (i.e., low cART adherence, episodes of cART interruption, non-optimal cART regimen, short cART duration), and comorbidities (i.e., positive HCV serostatus with high HCV RNA, history of acute cardiovascular event and presence of cardiovascular risk factors, anemia, and thrombocytopenia). The gene discussed is CD4; the disease is anemia (phenotype).