Human immunodeficiency virus (HIV) and SARS-CoV-2 are almost nothing alike, but the response to the COVID-19 pandemic has much to learn from four decades of efforts against HIV and AIDS. It took decades of research on issues that are not at all associated with a coronavirus before prototype COVID-19 vaccines could be developed in a matter of months [1]. HIV-1, a member of Retroviridae virus family, and SARS-CoV-2, a coronavirus of subgenus Sarbecovirus, are positive-sense single-stranded RNA viruses. Main difference between SARS-CoV-2 and HIV-1, however, is that most individuals infected with SARS-CoV-2 shed the virus, while those with HIV-1 do not [2]. This is because SARS-CoV-2 is a slowly mutating and non-integrating virus, and the host can rely on a secondary vaccine-initiated immune response to clear SARS-CoV-2 infected cells [3]. After natural infection with SARS-CoV-2, people living with HIV have lower concentrations of anti-spike IgG and pseudo-virus neutralizing antibody titres [4]. For other immunocompromising conditions, such as solid organ transplantation, decreased immunogenicity for SARS-CoV-2, a messenger RNA vaccine has been documented, with emerging data for other conditions [5].