Immunosenescence and Ageing in HIV

Living reference work entry

Abstract

HIV was the prime killer of youth and severely limited life expectancy until recently, when potent antiretroviral therapy reduced both morbidity and mortality. However, treatment did not normalize patient life span. Despite effective therapy, immune recovery is incomplete. Reconstitution of CD4 T cells occurs, but a residual altered immune phenotype persists with long-term clinical consequences. Death in these patients frequently occurs from the same comorbidities causing death in the elderly. Their lingering laboratory and clinical phenotype is very characteristic of immune ageing, a process that is referred to as immunosenescence.

HIV disease has been proposed as a model of accelerated immunosenescence. The mechanisms driving this acceleration are not clear and likely multifactorial. Host responses and attempts at restoration of immunity, as well as a long-term damaged immune environment, appear to be linked to ageing complications. During treatment with antiviral therapy, premorbid conditions not only remain but also find fertile ground to exploit the underlying compromised host landscape. The immune system, despite undetectable plasma HIV RNA, is not quiescent. A chronic subclinical inflammatory state often persists. It remains to be determined if this inflammation is driven by very low-grade expression of HIV antigens or by persistent antigenic challenge from secondary comorbidities or both. The net effect is the early emergence of a remodeled ageing phenotype with many of the features and impairments found in the very elderly. Although the mechanisms in HIV-associated immunosenescence are likely multiple and complex, growing evidence supports the concept that CMV plays a central role.

Keywords

Ageing Immune homeostasis Chronic inflammation Immunosenescence Comorbidities HIV CMV Immune risk phenotype 

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.McGill UniversityMontrealCanada

Section editors and affiliations

  • Tamas Fulop
    • 1
  1. 1.Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of MedicineUniversity of SherbrookeSherbrookeCanada

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