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Inflammation & HIV.....inflammation is the general population & in HIV+ is associated with non-AIDS comorbidities, so is immune activation
  Aging & Cure - a talk by Steve Deeks, MD at the IAS Conference in Kuala Lumpur......[will a cure ameliorate or reverse the years of damage from inflammation & immune activation in HIV+ individuals?
- Inflammation remains elevated during long-term ART although the elevation is moderate.
- A single measurement of markers IL6 or D-Dimer predicts mortality and morbidity
- Inflammation predicts disease/non-AIDS comorbidities (mortality/heart disease/lymphoma/diabetes/cognitove dysfunction/frailty) just as it does in general population, non-HIV infected......http://www.natap.org/2013/IAS/IAS_22.htm INTERVENTIONS: diet & exercise may be the best intervention, studies have proven they can reduce inflammation. That means a healthy diet, low fat, lots of vegs. The Mediterranean Diet has been reported in studies to reduce inflammation, perhaps slow the aging process---this is link to article in New England Journal of Medicine [http://www.natap.org/2013/newsUpdates/022713_01.htm]. A vegetarian based diet along with perhaps daily veg juicing has been used by many in the general population not necessarily exclusive or excluding protein like fish, chicken, soy. It is important to drink a lot of water daily for kidney health. Studies have implicated fat from meat in heart disease. Studies show exercise can reduce inflammation. Since inflammation is associated with comorbidities exercise & diet in that it reduces inflammation may reduce the risk for developing comorbidities - heart disease, cancers, frailty, cognitive impairment. Earlier start of HAART has been found to be associated with lower inflammation.
Published last week: Associations of Inflammatory Markers With AIDS and Non-AIDS Clinical Events After Initiation of Antiretroviral Therapy: AIDS Clinical Trials Group A5224s, a Substudy of ACTG A5202 - (01/21/14)......."In summary, we showed that higher levels of several inflammatory biomarkers were associated independently of CD4 with increased risk of AIDS or non-AIDS events.
......Higher baseline IL-6, sTNF-RI, sTNF-RII, and sICAM-1 were significantly associated with increased risk of AIDS-defining events
HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality.....Immunity, October 17, 2013.....Steven G. Deeks,1Russell Tracy,2and Daniel C. Douek3......http://www.natap.org/2013/HIV/101713_02.htm
In the general population, inflammation also contributes to the pathogenesis of many chronic medical illnesses, including cardiovascular and cerebrovascular disease (CVD), diabetes, chronic kidney disease, osteoporosis and cancer. These same illnesses, termed non-AIDS comorbidities (NACoMs) now account for most morbidity and mortality in people with HIV receiving virologically suppressive antiretroviral therapy (ART).......At CROI 2013, new studies were presented that consolidate that view and highlight the importance of activation of the monocyte/macrophage axis in cardiovascular disease pathogenesis and all-cause mortality
Immune Activation/inflammation markers IL-6 & D-dimer were discussed in the sense of their affect on nonAIDS events & death - heart disease http://www.natap.org/2013/CROI/croi_69.htm In the SMART/INSIGHT Cohort 262 patients experienced a serious non-AIDS event (SNA) or died: cancer 36%, CVD 26%, renal 3%, hepatic 8%, death, other non-AIDS 27%. Using Kaplan-Meier estimates of the cumulative % of patients who experience SNA/death wad overall 7% after 5 years followup. However, patients with the highest level of inflammation marker IL-6 experienced 12% SNA/deaths, and for inflammation marker D-dimer 10% with the highest level of this inflammation marker experienced SNA/death. A 2-fold higher IL-6 resulted in a 44% higher risk for SNA/death, and a 2-fold higher D-dimer resulted in a 25% higher SNA/death risk. Both markers together with 2-fold higher levels resulted in increased risk as well. She reports a 2-fold higher IL-6 & D-dimer score results in 60% greater risk for SNA/death, 37% increased risk for CVD, 51% increased risk for cancer, 188% increased risk for renal & liver disease, and a 100% increased risk for death, all-cause. Again this is data from the SMART/INSIGHT analysis.
HIV-Infected Adults Are at Greater Risk for Myocardial Infarction (MI), End-stage Renal Disease (ESRD), and Non-AIDS-defining Cancers, But Events Occur at Similar Ages Compared to HIV-uninfected Adults
Author Summary and Conclusions
Greater risk?
· HIV+ individuals had a greater rate of MI (81% increased risk for myocardial infarction), ESRD (43% increased risk for end-stage renal disease), and HIV- ssociated cancers (84% increased risk)
- Prevention (diet, exercise, smoking cessation, diabetes
control, etc.) and screening are critical in protecting the health of aging HIV+ adults
"levels of Inflammation Markers-- IL-6, soluble TNF receptors I & II, and soluble CD14 ( sCD14, a marker of monocyte activation) were significantly associated with clinical events"
"Previous studies have shown IL-6 and d-dimer levels to be among the most powerful predictors of future occurrence of NACoMs (non-AIDS events) and death"
---Soluble Markers of Inflammation & Coagulation, but not T-Cell Activation, Predict Non-AIDS Defining Events During Suppressive Antiretroviral Therapy (ART)....Non-AIDS Events: non-accidental non-AIDS death, MI, stroke, non-AIDS cancer, or serious non-AIDS bacterial infection http://www.natap.org/2013/CROI/croi_78.htm
A third study also highlighted the importance of elevated levels of soluble markers of innate immune activation. Tenorio et al. analyzed the ACTG cohort of ART trials participants in long-term follow-up to determine the relationship between soluble plasma markers of inflammation, cellular markers of T-cell activation and clinical events, defined here as MI, stroke, serious non-AIDS bacterial infections and non-accidental death [4]. Cases (n=143) who experienced an event were matched to 315 controls who did not. In multivariable analysis adjusted for multiple potential confounding characteristics, levels of IL-6, soluble TNF receptors I & II, soluble CD14 ( sCD14, a marker of monocyte activation) were significantly associated with clinical events, while markers of T-cell activation and senescence were not. This relationship was found at baseline (pre-ART) but also held at one year after initiating ART and in a time-updated analysis that used the last pre-event value. Although markers of T-cell activation were not correlated with clinical events, CD4+ T-cell immune reconstitution was. Compared to controls, cases had poorer CD4+ reconstitution and every 100 cell/uL increase in CD4 conferred a 19% reduction in risk of clinical events.
Immune Activation [as measured by CD16] Can Lead to Heart Disease: This study suggests that CVD in HIV-positive individuals may be a more aggressive disease with more features that lead to serious events, and that systemic inflammation, particularly involving innate immunity and the monocyte/macrophage axis is central to the pathogenesis.......Coronary heart disease in HIV-infected individuals may have more high-risk anatomic features and pathogenesis may be driven by monocyte activation, as suggested in an abstract presented by Zanni et al.......In univariate analysis, the presence of LAP [low-attenuation plaque] correlated with both traditional CVD risk factors and inflammatory markers, but only plasma levels of soluble CD163, a marker of monocyte activation, remained independently associated with LAP in multivariate analysis...coronary artery calcium (CAC) progression...monocyte expression of CD16, (with or without CD14, referred to as intermediate and non-classic monocyte phenotypes) were independently associated with CAC progression at two years.
Inflammation and HIV at CROI 2013: Focus on the Monocyte/Macrophage Axis and Innate Immunity - David H. Shepp, MD Associate Professor of Medicine Hofstra North Shore-LIJ School of Medicine North Shore University Hospital - Manhasset, NY - (03/11/13)
Systemic Effects of Inflammation on Health during Chronic HIV Infection - (10/17/13)
Immunity, October 17, 2013
Steven G. Deeks,1Russell Tracy,2and Daniel C. Douek3University of California, San Francisco, San Francisco, CA 94114, USA2University of Vermont, Colchester, VT 05405, USA3Vaccine Research Center, National Institutes of Health, Bethesda, MD
Interventions to Reduce Chronic Inflammation, Steven
Deeks.....http://www.natap.org/2013/IAS/IAS_22.htm.....HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality
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