HIV and the spectrum of human disease

Abstract

Infection with the human immunodeficiency virus (HIV) causes systemic T cell destruction and reduced cell-mediated immunity that leads to a wide range of opportunistic infections and cancers. Second, it directly damages many tissues -gut, brain, lung -through mononuclear cell infection and activation. Third, through immune activation and effects on endothelia, it can cause more subtle systemic organ damage, such as chronic cardiovascular, hepatic, pulmonary and central nervous system disease. Antiretroviral treatment has enabled HIV-infected persons to live with chronic infection, although with some side-effects and mortality, including reactions due to the immune reconstitution inflammatory syndrome (IRIS). As cohorts of infected people get older, age-related diseases will combine with chronic HIV infection to produce disabilities whose scale is not yet understood. HIV is detectable in tissues by immunohistochemistry when infection loads are high, such as at first presentation. Pathologists should proactively consider HIV disease in routine diagnostic work, so as to identify more HIV-infected patients and enable their optimal management.

The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells

“…A member of the immunoglobulin superfamily, CD4 interacts with major histocompatibility complex (MHC) class II receptor involved in antigen presentation, signal transduction, and T-cell activation in response to viral infection (2). In the context of HIV, the CD4 receptor and the chemokine receptor type 4 (CXCR4) function as coreceptors for viral entry into T helper cells – the primary mechanism leading to immune suppression, and, ultimately, acquired immune deficiency syndrome (AIDS) (4). Chemokine receptors, including CXCR4 and CCR5, play a broad role in viral pathogenesis, in part through the regulation of immune cell trafficking and effector functions (5).…”

“…With chronic HIV infection, the widespread activation of T cells and monocytes/macrophages is associated with proinflammatory cytokine production, increased viral replication, and cellular immune activation, which, over time, leads to suppressed innate and adaptive immune function and susceptibility to opportunistic infections and cancers (4). Moreover, persistent immune activation can promote proinflammatory processes involved in atherosclerotic cardiovascular disease and neurocognitive impairment, both of which are highly prevalent in HIV/AIDS (4, 7).…”

Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia

“…The patient did not have an HIV infection and did not have a history of cytotoxic/immunosuppressive therapy. Although her CD4+ cell count was not determined before chemotherapy, there were no other symptoms or test results suggestive of defective acquired cellular immunity, such as cytomegalovirus infection, tuberculosis, or herpes zoster (16). Based on these facts, AML is the only underlying disease to have triggered candidiasis in this patient.…”

The Immune Fulcrum

“…HIV-infected individuals remain infected for life, and most suffer consequent health complications including chronic immune activation and increased susceptibility to unrelated pathogens, cancers, and inflammatory disorders. 99 Correlates of protection against HIV acquisition and cure remain unknown, though some hints derived from rare individuals who are refractory to HIV acquisition or progress significantly more slowly than average remain an intensive area of interest. 100–104 In this regard, a role for Tregs in HIV acquisition and disease progression is multifaceted.…”