HIV as a Cause of Immune Activation and Immunosenescence

Abstract

Systemic immune activation has emerged as an essential component of the immunopathogenesis of HIV. It not only leads to faster disease progression, but also to accelerated decline of overall immune competence. HIV-associated immune activation is characterized by an increase in proinflammatory mediators, dysfunctional T regulatory cells, and a pattern of T-cell-senescent phenotypes similar to those seen in the elderly. These changes predispose HIV-infected persons to comorbid conditions that have been linked to immunosenescence and inflamm-ageing, such as atherosclerosis and cardiovascular disease, neurodegeneration, and cancer. In the antiretroviral treatment era, development of such non-AIDS-defining, age-related comorbidities is a major cause of morbidity and mortality. Treatment strategies aimed at curtailing persistent immune activation and inflammation may help prevent the development of these conditions. At present, the most effective strategy appears to be early antiretroviral treatment initiation. No other treatment interventions have been found effective in large-scale clinical trials, and no adjunctive treatment is currently recommended in international HIV treatment guidelines. This article reviews the role of systemic immune activation in the immunopathogenesis of HIV infection, its causes and the clinical implications linked to immunosenescence in adults, and the therapeutic interventions that have been investigated.

In Human Immunodeficiency Virus primary infection, early combined antiretroviral therapy reduced γδ T‐cell activation but failed to restore their polyfunctionality

“…During HIV infection there is a general activation of the immune system . We investigated the activation profile of γδ T cells in EPI and LPI groups by flow cytometry.…”

Beneficial and Detrimental Effects of Antiretroviral Therapy on HIV-Associated Immunosenescence

“…The subsequent microbial translocation from the gastrointestinal tract to the systemic circulation is only partially reduced in patients receiving effective therapy [112-114]. The HIV-associated strong increase in IFN-α, IFN-γ, TNF-α, and IL-6 [115] also causes a profound depletion of CD4+ cells from the gut that is incompletely reversed by ART [114]. On the other hand, Keating et al [63, 110], aiming at describing the qualitative and quantitative nature of cytokine perturbation, reported that treatment-naive HIV patients have decreased serum levels of IL-15 and IL-12 as well as IFN-γ inducible protein-10 (IP-10) and TNF-α, while HAART-treated patients showed cytokine profiles more similar to those observed in uninfected individuals.…”

Systemic inflammation and risk of age-associated diseases in people living with HIV on long term suppressive antiretroviral therapy

“…It has been reported that certain age-related NICMs like diabetes mellitus, cardiovascular disease, cancer, bone fracture and renal failure, are more common among HIV-1 infected individuals as compared to the general population. Exposure to prolonged cART along with low grade inflammation and persistent immune activation seen in HIV-infection is thought to be the cause for the increased risk of NICMs [2,10]. Chronic inflammatory conditions and persistent immune activation are believed to be the major drivers of aging physiology.…”

“…Though treatment successfully controls HIV-replication and prevents opportunistic infections, HIV-infected persons on long term ART not only succumb to death at an earlier age than the HIVuninfected counterparts but also suffer from some maladies that are typically associated with human aging (Deeks, 2011). The effect of HIV-associated inflammation and immune activation on premature onset of immunosenescence despite effective viral suppression are thought to be the primary reasons for early aging in people living with HIV (PLHIV) (Sokoya et al, 2017).…”