The immune response to SARS-CoV-2 in people with HIV

Abstract

This review examines the intersection of the HIV and SARS-CoV-2 pandemics. People with HIV (PWH) are a heterogeneous group that differ in their degree of immune suppression, immune reconstitution, and viral control. While COVID-19 in those with well-controlled HIV infection poses no greater risk than that for HIV-uninfected individuals, people with advanced HIV disease are more vulnerable to poor COVID-19 outcomes. COVID-19 vaccines are effective and well tolerated in the majority of PWH, though reduced vaccine efficacy, breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in PWH. This is likely a result of suboptimal humoral and cellular immune responses after vaccination. People with advanced HIV may also experience prolonged infection that may give rise to new epidemiologically significant variants, but initiation or resumption of antiretroviral therapy (ART) can effectively clear persistent infection. COVID-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWH who are moderately to severely immunocompromised. We recommend continued research and monitoring of PWH with SARS-CoV-2 infection, especially in areas with a high HIV burden.

Keywords: HIV; Immune dysfunction; Immunogenicity; Prolonged infection; SARS-CoV-2; Vaccine efficacy.

Fig. 1

HIV-associated immune dysregulation. In the early stages of HIV infection, a rapid burst of viral replication leads to rapid depletion of mucosal CD4+ T cells. Slower and progressive depletion of CD4+ T cells in peripheral tissues and blood ensues. HIV has a major impact on gut-associated lymphoid tissue and disrupts intestinal epithelial integrity, resulting in microbial translocation and onset of chronic immune activation and inflammation. This persistent immune activation further contributes to progressive depletion of CD4+ T cells, leading to alterations in T-cell phenotype and promotion of T-cell exhaustion. HIV infection also damages the fibroblastic reticular cell network within lymphoid tissues (LTs), affecting LT architecture and subsequently impacting germinal center reactions. The cumulative effect of HIV on the immune system compromises the capacity of the host to effectively coordinate immune responses against other pathogens or respond optimally to vaccines

Fig. 2

Immune responses to SARS-CoV-2 infection in PWH depend on their immune competency. PWH with well-controlled HIV infection (effective ART) show a humoral and T-cell response comparable to HIV-uninfected individuals, as characterized by strong T-cell and antibody response targeting multiple regions across the SARS-CoV-2 viral genome. Conversely, in ART-naïve individuals with low CD4 counts, generation of T-cell responses is suboptimal and of reduced frequency. Antibody responses are also compromised, likely due to HIV-induced changes in the architecture of lymph nodes, skewing the B-cell response toward an extrafollicular pathway. The suboptimal nature of the immune response in this context may lead to delayed clearance of SARS-CoV-2, creating an environment conducive to viral evolution. ART antiretroviral therapy, NCD noncommunicable diseases, OI opportunistic infections, LN lymph node, GC germinal center, Sw Switched memory B cells (IgD-CD27+), DN IgD-CD27- double negative B cells