Cytomegalovirus Seropositivity Is Associated With Increased Microbial Translocation in People Living With Human Immunodeficiency Virus and Uninfected Controls

Abstract

Background Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation. Methods A total of 150 PLWH (79 ART-naive and 71 ART-treated) were compared to 26 without human immunodeficiency virus (HIV) infection (uninfected controls). Plasma markers of HIV disease progression, epithelial gut damage, microbial translocation, nonspecific B-cell activation, anti-CMV and anti–Epstein-Barr virus (EBV) IgG levels, and proinflammatory cytokines were measured. Results CMV seropositivity and elevated anti-CMV IgG levels were associated with markers of epithelial gut damage, microbial translocation, and inflammation in PLWH and participants without HIV infection. In contrast, total nonspecific IgG, immunoglobulin M, immunoglobulin A, and anti-EBV IgG levels were not associated with these markers. CMV seropositivity was associated with markers of epithelial gut damage, microbial translocation, and inflammation independent of sociodemographic and behavioral characteristics of the study population. Conclusions CMV-seropositive people with and without HIV had increased epithelial gut damage, microbial translocation, and inflammation. Furthermore, anti-CMV IgG levels were independently associated with increased epithelial gut damage and microbial translocation. CMV coinfection may partially explain persistent gut damage, microbial translocation, and inflammation in ART-treated PLWH.

CD4+:CD8+ T Cell Ratio Normalization and the Development of AIDS Events in People with HIV Starting Antiretroviral Therapy

“…4,7,9,[25][26][27] Furthermore, our analyses may be restricted by the lack of information on several unmeasured confounders in UK CHIC known to modulate immune responses, including infection by cytomegalovirus and other human herpesvirus, tobacco, and alcohol use. [28][29][30][31][32] Finally, the small number of new AIDS events in the study means that our analyses may be underpowered to detect some associations.…”

The Bacterium Akkermansia muciniphila: A Sentinel for Gut Permeability and Its Relevance to HIV-Related Inflammation

“…Antiretroviral therapy (ART) has transformed the lives of PLWH by rapidly controlling viral replication and allowing CD4 recovery, reducing morbidity and mortality. However, despite controlling viral load and CD4 Tcell count, long-term ART reduces but does not normalize gut dysbiosis, microbial translocation, immune activation and inflammation (12)(13)(14). In addition to HIV itself, coinfection with cytomegalovirus or viral hepatitis, leaky gut and microbial translocation also lead to inflammation which has been associated with the risk of non-AIDS comorbidities (13,(15)(16)(17)(18).…”

“…However, despite controlling viral load and CD4 Tcell count, long-term ART reduces but does not normalize gut dysbiosis, microbial translocation, immune activation and inflammation (12)(13)(14). In addition to HIV itself, coinfection with cytomegalovirus or viral hepatitis, leaky gut and microbial translocation also lead to inflammation which has been associated with the risk of non-AIDS comorbidities (13,(15)(16)(17)(18). The direct influence of dysbiosis, microbiota by-products, epithelial barrier and local immune response will need further studies to define their distinctive role on systemic inflammation and subsequent development of non-AIDS comorbidities.…”

The Architecture of Circulating Immune Cells Is Dysregulated in People Living With HIV on Long Term Antiretroviral Treatment and Relates With Markers of the HIV-1 Reservoir, Cytomegalovirus, and Microbial Translocation

“…A small proportion of these cells remains latently infected with replication competent virus and defective proviruses, called the HIV-1 reservoir (13). The HIV-1 reservoir and increased microbial translocation, together with lifestyle factors and co-infections such as cytomegalovirus (CMV) may all contribute to the disrupted immune function in PLHIV (10,(13)(14)(15)(16)(17). However, published data have shown inconsistent or even contradictory findings.…”