Aging of the human innate immune system in HIV infection

Zapata, Heidi J.; Shaw, Albert C.

doi:10.1016/j.coi.2014.06.007

Cited by 30 publications

(30 citation statements)

References 109 publications

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“…Our finding of a “premature” aging trajectory is relevant to the ongoing discussions regarding the possibility that infection with HIV results in an accelerated or premature aging (see [30–32] for reviews). HIV disease moved individuals away from the healthy and unhealthy profiles, and towards the premature aging profile.…”

Section: Discussionmentioning

confidence: 73%

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study

Molsberry

Lecci

Kingsley

et al. 2015

Aids

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Objective The longitudinal trajectories that individuals may take from a state of normal cognition to HIV-associated dementia are unknown. We applied a novel statistical methodology to identify trajectories to cognitive impairment, and factors that affected the “closeness” of an individual to one of the canonical trajectories. Design The Multicenter AIDS Cohort Study (MACS) is a four-site longitudinal study of the natural and treated history of HIV Disease among gay and bisexual men. Methods Using data from 3,892 men (both HIV-infected and uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed Membership Trajectory Model (MMTM) was applied to capture the pathways from normal cognitive function to mild impairment to severe impairment. MMTMs allow the data to identify canonical pathways and to model the effects of risk factors on an individual’s “closeness” to these trajectories. Results We identified three distinct trajectories to cognitive impairment – one “normal aging” (low probability of mild impairment until age 60), one “premature aging” (mild impairment starting at age 45–50), and one “unhealthy” (mild impairment in 20s and 30s) profile. Second, clinically defined AIDS and not simply HIV Disease, was associated with closeness to the premature aging trajectory. And, third, Hepatitis-C infection, Depression, Race, Recruitment Cohort and Confounding Conditions all affected individual’s closeness to these trajectories. Conclusions These results provide new insight into the natural history of cognitive dysfunction in HIV disease and provide evidence for a potential difference in the pathophysiology of the development of cognitive impairment based on trajectories to impairment.

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Section: Discussionmentioning

confidence: 73%

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study

Molsberry

Lecci

Kingsley

et al. 2015

Aids

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“…Inverted CD4:CD8 ratio together with loss of both naïve CD4 and CD8 T cells, expansion of activation and senescence markers on CD4 and CD8 T cells are presented both in HIV infection and ageing [52]. Differences in T cell compartments may echo changes observed in premature ageing associated with HIV infection [53]. The relationship of chronic inflammation, aberrant T cell function and phenotype as related to biologic ageing in HIV infection needs further investigation.…”

Section: Resultsmentioning

confidence: 99%

CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV‐positive patients

Lü¹,

Mehraj²,

Vyboh³

et al. 2015

Journal of the International AIDS Society

184

129

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IntroductionAbsolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients.MethodWe conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection.DiscussionLow CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults.ConclusionThe CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials.

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“…1). HIV infection leads to potent dysregulation and activation of the innate immune system through toll-like receptor activation, microbial translocation through gut CD4+ T cell and lymphoid tissue depletion and alteration in the gut microbiome, facilitation of co-infections, and promotion of cell death [95–97]. Even with cART, residual inflammation and immune cell activation persist and have been associated with increased morbidity and mortality among HIV-infected persons [95, 98, 99].…”

Section: Introductionmentioning

confidence: 99%

Frailty in HIV: Epidemiology, Biology, Measurement, Interventions, and Research Needs

2016

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Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stressors, predisposing to major adverse clinical outcomes, including hospitalization, institutionalization, disability, and death in the general population of older adults. As the proportion of older adults living with HIV increases in the era of antiretroviral therapy, frailty is increasingly recognized to be of significant clinical and public health relevance to the HIV-infected population. This article reviews current knowledge on the epidemiology and biology of frailty and its potential role as a target for reducing disparities in outcomes in HIV; conceptual frameworks and current approaches to frailty measurement; existing data on frailty interventions; and important areas for future research focus necessary to develop and advance effective strategies to prevent or ameliorate frailty and its marked adverse consequences among people living with HIV.

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Aging of the human innate immune system in HIV infection

Cited by 30 publications

References 109 publications

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study

CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV‐positive patients

Frailty in HIV: Epidemiology, Biology, Measurement, Interventions, and Research Needs

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