Cytomegalovirus and HIV: A Dangerous Pas de Deux

Abstract

Human immunodeficiency virus (HIV)-infected adults who take stable antiretroviral therapy (ART) are at risk for early onset of age-related diseases. This is likely due to a complex interaction between traditional risk factors, HIV infection itself, and other factors, such as underlying immune dysfunction and persistent inflammation. HIV disrupts the balance between the host and coinfecting microbes, worsening control of these potential pathogens. For example, HIV-infected adults are more likely than the general population to have subclinical bursts of cytomegalovirus (CMV) replication at mucosal sites. Production of antigens can activate the immune system and stimulate HIV replication, and it could contribute to the pathogenesis of adverse outcomes of aging, like cardiovascular disease and neurocognitive impairment. Further investigation of the relationships between CMV, immune dysfunction, and unsuccessful aging during chronic HIV infection is warranted.

Keywords: HIV; aging; cytomegalovirus; end organ disease; immune dysfunction; inflammation.

Figure 1.

Proposed model connecting cytomegalovirus (CMV), human immunodeficiency virus (HIV), immune dysfunction and worse disease outcome. HIV infection induces CD4⁺ T cell loss and dysfunction, thereby failing to provide help to CD8⁺ T cells and permitting more CMV replication. Both viral infections contribute to inflammation, immune senescence and promote the expansion of CD8⁺ T cells. Such CD8⁺ T cell expansion, coupled with a loss of CD4⁺ T cells (leading to a lower CD4/CD8 T cell ratio) are linked to morbid outcomes of CMV and HIV infections. Additionally, CMV might cause direct cellular damage to endothelial cells and other cell types further contributing to end organ damage.