Dynamics of HIV reservoirs following repeated anti-SARS-CoV-2 vaccination

Due to persistent immune dysfunction, People with HIV (PWH) are at increased risk of more severe infections with SARS-CoV-2 and hospitalizations. In several countries, they were listed as a priority group for receiving anti-SARS-CoV-2 vaccines when these vaccines were in scarce supply. These prophylactic vaccines do not completely prevent infections in vaccinated individuals, especially with a heterologous vaccine strain. However, they persistently reduce the severity of breakthrough infections, hospitalization rates and deaths. Although antiretroviral therapy (ART) suppresses HIV replication below the levels detectable by the assays used routinely in clinical care, it does not eliminate viral reservoirs; a small pool of infected cells carrying HIV proviruses integrated into the genomes of CD4⁺ T cells and a subset of myeloid cells. Since vaccines work by stimulating these cells, they may theoretically reactivate latent HIV, increase plasma viremia and modulate the size of the HIV reservoir. The apprehension of HIV reactivation in PWH on ART prompted several studies in the past five years to investigate the impact of anti-SARS-CoV-2 vaccination on the markers of HIV persistence. Collectively, these studies have shown that the vaccination is generally safe in PWH on ART and induces only transient increases in viremia with no measurable impact on the size of the reservoir. However, in PWH with unsuppressed viremia, the vaccination was accompanied by more prolonged increases in viremia and in the frequencies of HIV-infected cells. In this review, we discuss these studies, their outcomes, their implications for HIV cure and propose topics for further research.