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Persistent inflammation in chronic HIV infection may affect immune responses against SARS-CoV-2 infection. Plasma levels of multiple proinflammatory cytokines during acute SARS-CoV-2 infection were assessed in people with HIV (PWH) with effective cART. There were no significant differences in any of the tested cytokines between COVID-19 severity in PWH, while most of them were significantly higher in individuals with severe disease in HIV-uninfected individuals, suggesting that excess cytokines release by hyper-inflammatory responses does not occur in severe COVID-19 with HIV infection. The strong associations between the cytokines observed in HIV-uninfected individuals, especially between IFN-α/TNF-α and other cytokines, were lost in PWH. The steady state plasma levels of IP-10, ICAM-1, and CD62E were significantly higher in PWH, indicating that PWH are in an enhanced inflammatory state. Loss of the several inter-cytokine correlations were observed in in vitro LPS stimuli-driven cytokines production in PWH. These data suggest that inflammatory responses during SARS-CoV-2 infection in PWH are distinct from those in HIV-uninfected individuals, partially due to the underlying inflammatory state and/or impairment of innate immune cells.

Virus-specific CD8+ cytotoxic T lymphocyte (CTL) responses play an important role in the control of immunodeficiency virus infections. Therapeutic immunization with antigen-pulsed dendritic cells (DC) may be a promising strategy for stimulating CTL. However, decreases in DC number and function have been suggested in the host persistently infected with the virus, and this may constitute an obstacle to DC-based immunotherapy in the chronic phase. In this study, we show that virus-specific CTL responses were augmented by therapeutic immunization with inactivated virus-pulsed autologous DC in rhesus macaques that had maintained prophylactic vaccine-based control of virus replication for more than 3 years after simian or simian-human immunodeficiency virus challenge. Our results indicate the potential of DC in the chronic phase for efficiently stimulating CTL in vivo, suggesting the feasibility of therapeutic DC immunization for replenishing virus-specific CTL responses in the chronic phase after the prophylactic vaccine-based control of primary immunodeficiency virus infection.