jules levin, NATAP: research links & notes on HIV/AIDS, aging, frailty & multimorbidities (035)


there’s quite a bit here.

jules is following up on a 2007 NIH workshop on HIV/AIDS & aging, observing that “since then …[not] much [has] been done to address the issues & questions raised in the CID report of the meeting.”

i intend to skim & study this just as much to get a handle on the terminology as to get a sense of the terrain from my point of view, a PWA living in an assisted care institution.


Aging & HIV Recognized as a Serious Concern But No Real Discussion, Still Ignored. 2007 NIH Workshop recommendations
Jules Levin, NATAP

“by 2015 more than 50% of HIV+ will be >50 yrs old”. In 2007 the NIH held a workshop on aging but since then have you heard about the results? Has much been done to address the issues & questions raised in the CID report of the meeting linked to below? The report suggests guidelines should address these issues but they still don’t, there is no education for clinicians and patients, there was no mention of bone disease in the report from the workshop.

NIH Workshop on HIV in Older Adults Oct 20 2007 (selected slides) NIH Workshop on HIV in Older Adults Oct 20 2007. summary-1.gif. frailty-2.gif … Discussion Topic I: Overarching Issues in HIV and Aging Research … www.natap.org/2009/HIV/081909_01.htm

Consequences of the future of aging with HIV / Treatment / Global …Jul 8, 2009 … If aging with HIV develops into a serious problem which many think it is … forfrailty among HIV+ individuals in mACS compared to HIV-negatives. … liver disease for HBV/HIV coinfected patients. By Jules Levin. NATAP … www.eatg.org/…HIV…/Consequences-of-the-future-of-aging-with-HIV

HIV-1 Infection Is Associated With an Earlier Occurrence of …FrailtyConsequences of the Future of Aging with HIV The MACS group has published increased risk of up to 15 times for frailty among HIV+ individuals in mACS … www.natap.org/2009/HIV/071809_03.htm

TPAN || Test Positive Aware Network || HIV InformationOsteoporosis is associated with increased frailty and mortality. … “Aging with HIV” by Victor Valcour, M.D. on page 37. Visit http://www.natap.org. back to top … positivelyaware.com/2009/09…/hiv_accelerates_aging.shtml

HIV infection, antiretroviral treatment, ageing, and non-AIDS …Published 26 January 2009, doi:10.1136/bmj.a3172 Cite this as: BMJ 2009;338: a3172. Steven G Deeks, professor of medicine1, Andrew N Phillips, professor of … www.natap.org/2009/HIV/012809_05.htm

AGING AND INFECTIOUS DISEASES- NIH-NIAID Workshop on HIV Infection … AGING AND INFECTIOUS DISEASES- NIH-NIAID Workshop on HIV Infection and Aging: What Is Known and Future Research Directions … www.natap.org/2008/HIV/072508_05.htm Clinical Infectious Diseases July 2008

“The presence of multimorbidities, including medical, psychiatric, and substance use comorbidities, is more common in HIV-infected patients than in uninfected patients [64], but primary care guidelines rarely account for comorbid conditions [153-165]. Current strategies for prioritizing multimorbidities do not account for clinical dominance and concordance of conditions or for the presence or absence of symptoms….few drug trials involving aging populations have been performed

Available Cohorts and Resources for Research in Aging and HIV Infection: NA-ACCORD…NA-ACCORD cohorts with the oldest populations are the Veterans Aging Cohort Study, the Multicenter AIDS Cohort Study, and the AIDS Link to the Intravenous Experience. The Veterans Aging Cohort Study was designed to evaluate issues of HIV infection specifically in older veterans.

“by 2015, more than one-half of all HIV-infected individuals in the United States will be aged >50 years….Both aging and HIV infection are associated with profound changes in immunity and host defense, with marked similarities and some differences (table 1). The T cell compartment, particularly in the gastrointestinal tract, is most disrupted by HIV infection and aging, but nearly all aspects of immunity are affected…..Clinical evidence of B cell dysfunction is apparent in both HIV-infected and older adults…..The thymus involutes both with age [24] and with HIV infection…Eventually, the cells reach replicative senescence [29-32], with short telomeres, very low telomerase activity, and production of high levels of proinflammatory cytokines. These cells work through bystander mechanisms to accelerate memory cell turnover and death [33] and to impede maturation and/or proliferation of naive T cells….Mucosal host defenses are profoundly affected by HIV infection….replicative senescence and immunologic changes in CTLs occur in older HIV-uninfected adults….The consequences of T cell senescence are profound, and loss of previous control over chronic viral infections is apparent

Conceptually, frailty is a state of decreased physiologic reserves that increases patient risk of morbidity and mortality….HIV infection appears to accelerate frailty [98]; even while receiving HAART…..Frailty predicts poor health outcomes in uninfected individuals…..The mechanism(s) of frailty is unknown, but increases in the number of free radicals, mitochondrial dysfunction, and cytokines may activate inflammatory pathways, leading to frailty…..Levels of C-reactive protein, D-dimer, factor VIIII, fibrinogen, and IL-6 are elevated in older people with the frailty phenotype [105-107], and these increased levels are associated with frailty intermediates (e.g., wasting) in HIV-infected adults [108, 109]. Likewise, HIV infection and drug toxicities activate frailty-associated inflammatory pathways

Advanced HIV disease and hepatitis C virus (HCV) coinfection increase the risk of chronic kidney disease [133], and HCV coinfection, lower CD4+ T cell count, drug toxicity, and liver disease have been associated with acute renal failure

Liver disease is second only to direct AIDS-related complications as a cause of death in HIV-infected patients (figure 4), with up to a 4-fold increase in hepatic morbidity and mortality among older patients, compared with young adults….Mortality associated with liver disease is high among HIV-infected patients, even in the HAART era [140, 137]. Coinfection with HIV increases the likelihood of cirrhosis in patients with hepatitis [64, 141]. HIV infection is not associated with hepatocellular cancer, but age is associated with this condition [142]…..10%-20% of HIV-infected patients are also positive for hepatitis B surface antigen [143-147], and hepatitis B disease-associated mortality is increased among men with HIV and hepatitis B coinfection….Immune dysfunction in HIV-HCV-coinfected patients differs from that associated with chronic HIV or HCV infection alone [148-150], and some comorbidities are more common among coinfected individuals [148]. Age and kidney function influence the effectiveness and tolerability of HCV treatment [151], and age is an independent risk factor for anemia in patients treated for HCV infection

HIV infection and specific antiretroviral drugs contribute differentially to fat and metabolic changes associated with increased risk of CVD. Both aging and HIV infection are associated with muscle loss, but the type of fat loss differs between aged and HIV-infected individuals

HIV infection is associated with less insulin resistance [125], but specific antiretroviral drugs have a direct adverse effect on glucose metabolism……In one study, the incidence of diabetes or hyperglycemia was 4-fold higher in HIV-infected men than in uninfected men [128]

Kidney function is low both in elderly patients and in HIV-infected patients, affecting drug clearance, risk of drug toxicity, and mortality associated with cardiovascular events…..The incidence of kidney disease among HIV-infected individuals is increasing with age….the spectrum of kidney disease among older adults and the impact of comorbidities on kidney disease are poorly defined, particularly in HIV-infected patients. Accurate methods of measuring glomerular filtration rate have not been established for these populations

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