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Complications & It's Immunopathogenesis
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Reported by Jules Levin
CROI 2016 Feb 22-24 Boston
Aging/HIV IGNORED....The aging survivors left behind by AIDS - (03/09/16)
Unraveling the Complexities of Long Term Complications of Treated HIV Infection
Judith S. Currier
David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
She reviews global epidemiological trends in comorbidities, with a focus on cardiovascular disease & fat tissue (visceral adiposity)
WEBCAST to Judy Currier
talk: http://www.croiwebcasts.org/console/player/29407?mediaType=audio&
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Immunopathogenesis of Metabolic Complications in Treated HIV Infection.....
Microbial translocation, HIV persistence & coinfections cause persistent innate innate immune activation, as well as CD8 t-cell activation & increased gut permeability (leaky gut spilling out microbes) associated with visceral adiposity!, in patients with virologic suppression & all may play a role in immune activation, inflammation & consequent metabolic dysregulation & end organ disease...and how NASH, fatty liver is an inflammatory disease, which can cause liver fibrosis, all of which can develop as well as a result of these abnormalities. Talk concludes with review of how these metabolic pathways may provide potential targets for interventions that are under investigation to which one of my responses is - really?. She includes in her conclusions: "most innate immune activation is derived from the gut (microbial translocation +/- altered gut micro biome & these systemic changes are likely to underpin the development of metabolic complications in HIV+..."
from Jules: discussed - HIV causes abnormal glucose metabolism which may be associated along with mitochondrial dysfunction with frailty & comormid metabolic complications & Crowe discusses immune activation in HIV is associated with metabolic abnormalities & cormorbidities
Suzanne M. Crowe
Burnet Institute, Melbourne, Australia
WEBCAST:http://www.croiwebcasts.org/console/player/29682?mediaType=audio&
Dr Crowe discusses immune activation and persistence despite viral suppression
and take note of her slide...HIV Infection & normal aging......and these shared immunologic changes are likely to underlie in the increased comorbidities in HIV...she discusses activation markers in the blood and the accumulation of HIV in tissues which produce pro inflammatory cytokines, they accumulate in the colon (intestinal mucosa) being secreted by macrophages, and this persist in patients with virologic suppression over 4-17 years vs HIV-uninfected controls, and this immune activation can be associated with cardio metabolic disease or at least makers thereof. She also reviews data that HIV increases glucose metabolic activity in monocytes not restored by treatment with ART; she discusses inflammation implicated in comorbid metabolic diseases, she discusses what we know that inflammation in visceral adiposity in HIV+ persists. She discusses oxidative stress in HIV+ and its persistence, OX (oxidative stress) LDL & correlation with activation markers (IL-6, sCD14, sCD163 etc); frail HIV+ had significant mitochondrial dysfunction in patients with suppressed viral load and she refers to poster at CROI by D Chow suggested frailty is in part due to metabolic abnormalities in HIV.
She discusses HIV+ & normal aging people share immunologic abnormalities!
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A few relevant studies at CROI 2016:
Neurotoxicity Screening of Antiretroviral Drugs With Human iPSC-Derived Neurons - (03/10/16)
START Study - Immediate ART in START Cuts Risk of Infection-Linked Cancer About 75%
Results from all 4 physical performance tests showed significantly impaired performance when compared to normal reference ranges for HIV-uninfected adults matched by age and gender.....Older HIV-infected persons have diminished physical performance compared to HIV-uninfected controls.....http://www.natap.org/2016/CROI/croi_137.htm
60% frailty among 50-59 year old HIV+....39% pre-frail among 40-49 years old HIV+....http://www.natap.org/2016/CROI/croi_59.htm
Excess Mortality Among HIV-Infected Cancer Patients in the United States ....excessive breast cancer mortality found in young non-White females 30-49 & 50-69 years old Table 1) - (03/08/16)
STROKE
Incidental Carotid Plaque in HIV and an increase in subsequent Cerebrovascular Events.....Carotid Plaque Develops More Often With HIV and Triples Stroke Risk
STROKE INCIDENCE HIGHEST IN WOMEN AND BLACK HIV-INFECTED PARTICIPANTS IN ALLRT COHORT - (02/26/16)
Narrowing the gap in life expectancy for HIV+ compared with HIV- individuals...Life Expectancy Gap Between HIV+ and HIV- Narrows But Persists
Early Antiretroviral Therapy Does Not Improve Vascular Function: A START Substudy - (02/29/16)
Changes in CVD Risk Factors with Immediate and Deferred ART in the START Trial - (03/07/16)
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