Potential Impact of SARS-CoV-2 Spike Protein on HIV-1 Reservoir in People Living with HIV

People living with HIV-1 (PLWH) are part of the so-called "fragile" populations to which COVID-19 vaccines were/are strongly recommended. The fact that most widely used COVID-19 vaccines rely on the production of a biologically active SARS-CoV-2 Spike protein expressed by synthetic mRNA poses the relevant question of whether and how this vaccination influences the fate of the HIV-1 reservoir. This report presents a detailed analysis of the literature data on the effects of SARS-CoV-2 Spike and COVID-19 vaccines on HIV-1 latently infected cells. Despite being limited in number, the experimental evidences consistently indicate that vaccine mRNA and/or SARS-CoV-2 Spike can effectively reactivate latent HIV-1. This conclusion has been drawn after "in vitro", "ex vivo", and "in vivo" assays, and with virus-associated Spike, soluble Spike, or its intracellular expression, as well as with COVID-19 mRNA vaccines. On the other hand, real-world observations on vaccinated PLWH under antiretroviral therapy (ART) provided evidence of HIV-1 reactivation almost exclusively in PLWH with unsuppressed viremia, as measured in terms of size of the HIV-1 reservoir. Although several issues still need to be clarified through urgent additional investigations, these data suggest the possibility that the Spike protein and/or the vaccine mRNA molecules affect the HIV-1 latency in PLWH.