1 / 78

HIV and Aging: Accentuated Disease and Accelerated Aging KY AETC Annual Meeting March 29, 2014

Kevin P. High, MD, MS Professor of Medicine and Translational Science Chief, Section on Infectious Diseases Interim Chair, Department of Internal Medicine. HIV and Aging: Accentuated Disease and Accelerated Aging KY AETC Annual Meeting March 29, 2014. Outline.

hertz
Download Presentation

HIV and Aging: Accentuated Disease and Accelerated Aging KY AETC Annual Meeting March 29, 2014

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Kevin P. High, MD, MS Professor of Medicine and Translational Science Chief, Section on Infectious Diseases Interim Chair, Department of Internal Medicine HIV and Aging:Accentuated Disease and Accelerated AgingKY AETC Annual MeetingMarch 29, 2014

  2. Outline • Why study aging? – unparalleled “bang for the buck” • Intersection of the HIV Epidemic with Aging Research • Does HIV accelerate or accentuate aging? • Does it matter? • Mechanisms that may lead to premature multi-morbidity and functional decline in HIV • Priorities in HIV/Aging Research

  3. Non-aging survival curve for a wild animal • Why? • Predation • Disease • Habitat • Starvation • Accidental death • Risk of death same every year (50:50) • Animals do not appear to show signs of aging • Don’t live long enough in wild Slide courtesy of Neal Fedarko NSF JHMI

  4. As humans have increasingly controlled their environment, their life expectancy has  dramatically (“Rectangularization” of the survival curve) Slide courtesy of Neal Fedarko NSF JHMI

  5. “Rectangularization” of the Survival Curve: Median survival has about doubled Slide courtesy of Neal Fedarko NSF JHMI

  6. Miller, R. MillbankQuarterly Volume 80, Issue 1 (pages 155–174) 2002

  7. Slide courtesy of Jeff Halter

  8. “Rectangularization” of the Survival Curve: Required for median survival to triple NSF JHMI

  9. “It’s not the years, Honey, it’s the mileage . . . . .” Indiana Jones “You’re looking old Indy . . .” Marian

  10. JK • 1996 – 49 yo man initial Dx of HIV; no serious illness • With initiation of ART, BMI went from 22  29 • 1997-99 – one episode of bacterial pneumonia; some depression, occasional herpes keratitis • 2002 – hyperlipidemia • 2003 – diabetes mellitus diagnosed • 2004 – LE pain c/w neuropathy • 2005 – BPH severe enough to require TURP

  11. JK • 2006 – severe LLE pain  popliteal aneurysm requiring surgical repair • 2007 – constipation and rectal discharge  sigmoidoscopy  rectal carcinoma  surgery/XRT • 2009 – disabling sweats/hot flashes  venlafaxine, testosterone • 2012 – thoracic vertebral compression fracture

  12. JK • Treated with multiple ART’s over the years • zidovudine, didanosine, stavudine, abacavir, lamivudine, tenofovir, nevirapine, nelfinavir, ritonavir, fosamprenavir – VL nearly always undetectable • At least 7 morbidities developed from ages 52-64 • Diabetes, HTN, Hyperlipidemia, BPH, peripheral vascular disease, rectal carcinoma, fragility fracture • Became very depressed, lost his job, social isolation – complained of severe fatigue from day 1

  13. Eras of the HIV Epidemic Chu and Selwyn, J Urban Health. 2011 Mar 1. [Epub ahead of print]

  14. % of People Living with HIV over age 50 years Center for Quality Management in Public Health. The State of Care for Veterans with HIV/AIDS. Palo Alto, CA, USA2009 and CDC. Centers for Disease Control and Prevention. HIV Surveillance Report, vol. 21. http://www.cdc.gov/hiv/topics/surveillance/resources/reports/#surveillance; Published February 2011. Accessed August 2011.2009.

  15. AIDS and even most non-AIDS events (CVD, liver) have slowly declined, even during the late ART era

  16. 1 in 8 HIV-infected in Africa are over age of 50 Rates of co-morbidities higher in Botswana than US Community-based chronic care delivery models will be needed to address changing needs

  17. HIV and Aginghttp://www.frontiersla.com/Blog/FrontierBlog/blogentry.aspx?BlogEntryID=10304243%20&%20mid=50

  18. Concern in the popular press that HIV “accelerates” aging 59 year old man less “robust” than father HIV associated with multiple morbidities of aging France D. Another Kind of AIDS Crisis. New York. Nov 1, 2009 Gross G. AIDS Patients Face Downside of Living Longer. NY Times. Jan 6, 2008

  19. Acute MI in the VACS Cohort

  20. “Accelerated” Coronary Artery Aging in HIV infected patients > 40y (avg. HAART, 11 yrs) Avg. vascular age 15 yrs > chronologic age (based on MESA gender/ethnicity-specific curves) Guaraldi G, et al. ClinInfDis 2009;49:1756-62

  21. The risk for developing many morbidities remains higher than expected (~1.5 to 2.0 fold) even in those with “well-controlled” HIV Cardiovascular disease [1-3] Cancer (non-AIDS) [4] Bone fractures / osteoporosis [5,6] Liver disease [7] Kidney disease [8] Cognitive decline [9] Frailty (80% more common) [10] 1. Klein D, et al. J Acquir Immune DeficSyndr. 2002;30:471-477. 2; Hsue P, et al. Circulation. 2004;109:316-319. 3. Grinspoon SK, et al. Circulation. 2008;118:198-210. 4. Patel P, et al. Ann Int Med, 2008;148:728-736. 5. Triant V, et al. J ClinEndocrinolMetab. 2008;93:3499-3504. 6. Arnsten JH, et al. AIDS. 2007 ;21:617-623. 7. Odden MC, et al. Arch Intern Med. 2007;167:2213-2219. 8. Choi A, et al. AIDS, 2009;23(16):2143-49. 9. McCutchan JA, et a. AIDS. 2007 ;21:1109-1117. 10. Desquilbet L, et al. J Gerontol A BiolSci Med Sci. 2007;62:1279-1286; … Also reviewed in Hunt, Curr HIV/AIDS Reports, (2012) 9:139–147.

  22. Emerging Comorbid Diseases in HIV Age is a major risk factor for ALL of these co-morbidities

  23. Accelerated vs. Accentuated Aging

  24. Accelerated and Accentuated Aging

  25. Age at Onset of Cancer AIDS Patients and Age Matched Uninfected Individuals Shiels MS. Ann Intern Med 2010:153:452-460.

  26. HIV may not necessarily “accelerate” disease onsetHIV Increases risk of MI, ESRD and AIDS-associated cancer, but events occur at ~ same age (VACS cohort data) Althoff, et al, Abstract 59; Petoumenos, et al. Abstract 61

  27. Specific morbidities have different patterns of “aging” Possibly Accelerated Accentuation Accentuation Little Change Accentuation

  28. Swiss Cohort NB: most patients on 3 ARVs in addition to these medications, poly- pharmacy is the norm at 50 years. Hasse B. et al. CID 2011 53:1130-1139

  29. Obesity & Multi-morbidity in the 1917 clinic • 45% overweight or obese BEFORE initiating ART • “Metabolic” cluster (HTN, gout, DM, CKD) • “Behavioral” cluster (dyslipidemia, mood d/o’s, COPD, chronic ulcer dz, cardiac dz, OA, sleep apnea) • Substance Abuse cluster (Hep C, ETOH, substance abuse, tobacco abuse)

  30. HTN, Hyperlipidemia, prior MI HTN, Hyperlipidemia, prior MI

  31. Many definitions of frailty • Fried Frailty Phenotype (FFP) • Slowness, weakness, shrinking, inactivity, exhaustion) • 1-2 “pre-frail”, 3+ frail • Rockwood • Accumulated deficits/decreased reserve • Count number of conditions/lab abnormalities • Short Physical Performance Battery • Walking speed, chair stand, balance test

  32. Gait Speed predicts survival – even after fully adjusting for co-morbidity

  33. Gait Speed predicts survival – even after fully adjusting for co-morbidity

  34. VERY Robust across studies

  35. Pre-HAART Frailty and Persistence of Frailty Predict Survival

  36. Measuring Functional Impairment in PLWHErlandson, et al. HIV Clin Trials. 2012 Nov-Dec;13(6):324-34 • 359 participants (85% male, mean age 52 years, • mean CD4+ lymphocyte count 551 cells/µL) who were evaluated. • 3 - 8% low functioning • 31% -51% were moderate, and • 42% - 62% were high function. • FFP, SPPB, and 400-m walk test had moderate agreement for functional classification (61%-64%; κ = 0.34-0.41).

  37. Clinical Risk Factors for Functional Impairment Erlandson, et al. HIV Clin Trials. 2012 Nov-Dec;13(6):324-34 • Across instruments, the following NON-HIV RELATED risk factors were associated with lower function: • arthritis (OR ≯ 6.5; P < .02) • lower reported physical activity (OR ≯ 5.5; P ≤ .005) • debilitating pain (OR ≯ 5.4; P < .008) • no current employment (OR ≯ 4.2; P < .02) • more comorbidities (OR ≯ 3.6; P ≤ .005) • more non-antiretroviral therapy medications (OR ≯ 3.5; P ≤ .01) • psychiatric disease (OR ≯3.1; P < .03) • neurologic disease (OR ≯ 2.6; P < .05)

  38. Clinical Risk Factors for Functional Impairment Erlandson, et al. HIV Clin Trials. 2012 Nov-Dec;13(6):324-34 • Across instruments, the following HIV-related risk factors were associated with lower function: • Current CD4 <200 cells/µL (P = .04); • ALL other HIV-related characteristics were not significantly different (P > .05) on any instrument

  39. NEJM 2005; 352:48-62

  40. Lean mass and risk of low function P < 0.05 for all measures

  41. Fat mass and risk of low function P > 0.2 for all measures

  42. In a separate study with CT imaging frailty associated with intermuscular fat

  43. Bone density and risk of low function P = 0.028 P = 0.022 P = 0.093

  44. Serum hormone levels and risk of low function

  45. Potential inter-related pathways of aging with HIV leading to functional decline and frailty

  46. Risk factors for recurrent falls in PLWH

  47. Risk factors for recurrent falls in PLWH

  48. High rate of fractures in VACS Cohort

More Related