Kidney disease is a major complication of viral infection, which can cause both acute and chronic kidney diseases via different mechanisms such as immune-mediated injury, kidney cell injury from a direct viral infection, systemic effects, and antiviral drug-induced nephrotoxicity. HIV-associated nephropathy (HIVAN), characterized by collapsing focal segmental glomerulosclerosis (cFSGS), has been described 2 decades ago as a major complication of acquired-immunodeficiency syndrome. The pathogenesis of HIVAN has been well studied, including viral entry, host response, and genetic factors. The incidence of this disease has been dramatically dropped with current antiretroviral therapy. In the recent severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic, acute kidney injury was also found to be a major complication in patients with (coronavirus disease) COVID-19. These patients also developed glomerular disease such as cFSGS in African Americans with apolipoprotein L1 risk alleles, similar to HIVAN. Whether SARS-CoV-2 can infect kidney cells locally remains controversial, but both local infection and systemic effects are likely involved in the pathogenesis of this disease. In this review, we present a comparison of the clinical presentations, pathological findings, disease mechanisms, and potential treatments between HIVAN and COVID-19. Leveraging the knowledge in HIVAN and experimental approaches used to study HIVAN will facilitate the exploration in the pathogenesis of COVID-19-associated kidney disease and improve our management of COVID-19 patients.