It covers the similarities and differences between SARS-CoV-2 and HIV-1; delineates SARS-CoV-2-induced neurological manifestations, including learning from HIV-1-induced neurological outcomes; presents the risk factors of COVID-19 in PLWH and the neurological impact of SARS-CoV-2/COVID-19 and the HIV-1/AIDS syndemic; and explores plausible mechanisms underlying neurological sequelae in SARS-CoV-2 infection of PLWH and people with HAND focusing on the NLRP3 inflammasome overactivation-associated neurotoxicity [38,39]. This evidence concerns the gene NLRP3 and AIDS.