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HIV & Aging: Managing the Older Patient with HIV Infection

HIV & Aging: Managing the Older Patient with HIV Infection. Wayne McCormick, MD MPH 2013 AETC Asilomar Conference. HIV & Aging Consensus Panel. American Geriatrics Society American Academy of HIV Medicine AIDS Community Research Initiative of America J Applebaum [FSU], W McCormick [UW]

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HIV & Aging: Managing the Older Patient with HIV Infection

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  1. HIV & Aging: Managing the Older Patient with HIV Infection Wayne McCormick, MD MPH 2013 AETC Asilomar Conference

  2. HIV & Aging Consensus Panel American Geriatrics Society American Academy of HIV Medicine AIDS Community Research Initiative of America J Applebaum [FSU], W McCormick [UW] C Abrass [UW], C Boyd [JHU], S Braithwaite [NYU], VC Broudy [UW] K Covinsky [UCSF], K Crothers [UW], R Harrington [UW], K Gebo [JHU] K Goodkin [UCLA], R Havlik [NIA], W Hazzard [UW], K High [WFU] P Hsue [UCSF], M John [UCSF], A Justice [Yale], I McNicholl [UCSF] A Newman [Pitt], M Simone [Harvard], D Spach [UW], V Valcour [UCSF]

  3. Case 60 yo man HIV [X24y], Hx NHL, CAP depression, Afib, OSA, hyperlipidemia, hypothyroidism, HBP, DMII ,obesity, smokes 1 pack/week Diltiazem 240 mg QD / Lisinopril 2.5 mg QD / Warfarin 5 mg QD / Oxycodone 10 mg QID / Citalopram 20 mg QD / Metformin 500 mg BID / Levothyroxine 0.1 mg QD / Atazanavir+Ritonivir BID / Efavirenz/Emtricitibine/Tenofovir QD

  4. Case Exam: 220# , lungs clear, Corirreg VR 88 Abd considerable obesity, lipodystrophy CD4 = 177, VL undetectable FBS 280, A1C = 9.2, TSH 4 cholesterol 280, LDL 190 Recommended: Statins, Insulin

  5. Case Refused insulin. Started rosuvastatin after consulting with pharmacist, noting drug interaction w ARV. 2 months later: More depressed. Weight gain to 244 #.

  6. Case Cholesterol 498 Triglycerides 8700 A1C 10 Psychiatry, SW involved.

  7. Case Engaged in exercise (walking an hour a day) and naturopathic nutritional assessment and diet change: Subsequent weight in 5 months was 200# – FBS now 110, A1C 6.4 TG 660, Cholesterol 202, LDL 110 Still smoking rarely

  8. HIV & Aging Consensus Panel American Geriatrics Society American Academy of HIV Medicine AIDS Community Research Initiative of America 16 Panel Members – content consensus, section authors Modified Delphi Technique Meeting Washington DC 11/11 White House Conference 11/11 5 Staff from AGS / AAHIVM / ACRIA helped 6 Reviewers – reviewed document for face validity

  9. Objectives • Review Current Knowledge about HIV in older patients (Epidemiology, Clinical Outcomes w ART) • Discuss Aging Phenomena in HIV (T-cell Senescence, Multi-Morbidity, Aging [or Inflammatory] Acceleration, Frailty) • Cancer, CAD, & Advent of Non-AIDS health-related conditions in older patients with HIV • Psychosocial Issues / Advance Directives • Review findings of the Consensus Panel

  10. Faces of HIV Norma Martinez. Age: 61 HIV: 12 years lipodystrophy, fatigue Doug Turkington Age: 52 HIV: 20 years osteoporosis, two hip replacements. Enrico McLane Age: 52 HIV: 17 years Short-term memory loss two hip replacements Joe Westmoreland Age: 53 HIV: 27 years memory loss, fatigue, peripheral neuropathy in feet and hands Mike Weyand. Age: 58 / HIV: 20 years / osteoporosis, lipodystrophy, memory loss Photos courtesy of New York Magazine, Nov 2009 Cesar Figueroa /Age: 50 / HIV: 20 years dementia, neuropathy, depression Photos courtesy of New York Magazine, Nov 2009

  11. NA-ACCORDNorth American AIDS Cohort Collaboration on Research and Design Age US NA-ACCORD 18-19 3764 38 20-24 21197 468 25-29 39603 1164 30-34 54895 1863 35-39 83935 3128 40-44 121465 4765 45-49 128546 5455 50-54 94957 4236 55-59 57359 2658 60-64 28141 1345 >64 22103 910 US Trends in ARV Use AIM 157:325-35, 2012

  12. Clinical Outcomes in Older Patients Treated with ART • Virologic Suppression • Immunologic Response • Mortality

  13. Percent with VL suppression across time by Age Althoff IEDEA Feb 2010

  14. Percent with VL suppression across time by Age group and Regimen PIs NNRTIS Althoff K IEDEA Feb 2010

  15. Mean Increase in CD4 by Age 2 years after HAART Althoff K IEDEA Feb 2010

  16. Mean Increase in CD4 by age and regimen Boosted PIs NNRTIs

  17. Decline in Naïve T cell (CD4 and CD8) Compartment with Age Slide courtesy JorgGoronzy, MD

  18. Increased “senescent” T cells, particularly CD8; indicated by lack of CD28 expression Slide courtesy JorgGoronzy, MD

  19. % of CD8 cells that are CD28 negative highly correlated with influenza vaccine response Slide courtesy JorgGoronzy, MD

  20. Aging Reduces T cell Diversity Slide courtesy Jorg Goronzy, MD

  21. Immunosenescence • Immune system in older persons • Increased populations of terminally differentiated CD8 cells (CD28 negative) • Reduced level of naïve CD4 and CD8 cells, with reduced T cell proliferation • Increased T cell activation, with increased levels of inflammatory markers • Thymic insufficiency / failure • All are accelerated in HIV

  22. Residual Viral Replication Persistent virus expression (in LN) Collagen Deposition Microbial Translocation High pathogen load (CMV, HCV) Thymic dysfunction Residual Inflammation Immuno-senescence Suboptimal CD4 Gains Non-AIDS Events and Premature Mortality Adapted from Hsue CROI 2010

  23. HIV Outcomes: What we Know Already

  24. Non HIV Causes of Death Since ~2000

  25. Comorbidities Among Patients With HIV • Cancer: Non-AIDS-related malignancies • Neurologic / Cognitive Impairment • Endocrine: Early menopause, T deficiency • Bone disease: Osteoporosis / D deficiency Llibre JM. Curr HIV Res. 2009;7(4):365-377.

  26. 50 20 10 5 per 1000 pyrs (95% CI) Incidence 2 1 0.5 Age 65+ years Age 50-64 years 0.2 Age <50 years 0.1 Death Osteoporosis Diabetes mellitus Cerebral infarction AIDS defining event Bacterial pneumonia Myocardial infarction Pulmonary embolism Coronary angioplasty Fracture, adequate trauma Fracture, inadequate trauma Procedures on other arteries Non AIDS defining malignancies Incidence of comorbidities: by age B Haase CROI 2011

  27. Definitions • Comorbidity: additional diseases beyond the index disease • Multimorbidity: co-occurrence of diseases and functional consequences (the whole is worse than sum of the parts) = the aggregate burden of illness • Age, several conditions, function/cognition

  28. Impact of multimorbidity on 3-year decline in physical functioning Kriegsman et al. J Clin Epidemiol 2004;57:55-65

  29. Impact of multimorbidity on 3-year mortality Kriegsman & Deeg. In: Autonomy and well-being in the aging population 2 (1997)

  30. Incidence of Cancer in HIV-Infected Persons in the Post-HAART Era* *Patel, et al. Ann Int Med 2008;148:728-36

  31. Incidence of Cancer in HIV-Infected Persons in the Post-HAART Era* Interesting lack of increase in Breast or Prostate CA *Patel, et al. Ann Int Med 2008;148:728-36

  32. Median Age of Cancer Dx in General Population, AIDS Population and Adjusted General Populationp< 0.01 (obs vs. exp) for all shown Shiels, et al. Ann Int Med 2010; 153: 452-60

  33. Age at cancer diagnosis among people with AIDS and in the general population 1980-2006 • For most cancers: there is no difference in age at cancer diagnosis among persons with AIDS compared to the general population. Shiels CROI and AIM 2010

  34. Increasing Prevalence in Diabetes With Age in Both HIV-Infected and Non-Infected Populations • Medi-Cal database July 1994–June 2000 examined for diabetes mellitus (DM) age-specific incidence rates (DM diagnosed by ICD-9 codes) • 7219 HIV (61% male) and 2,792,971 non-HIV (30% male) individuals, for a total 7,101,180 person-years 14 HIV 12 Non-HIV 10 8 DM Incidence Rates (per 100 person-years) 6 4 2 0 18-24 25-34 35-44 45-54 55-64 65+ Age Group Currier J et al. 9th CROI; 2002; Seattle. Abstract 677.

  35. Accelerated Coronary Aging in HIV-infected patients > age 40 (avg. ART ~ 11 yrs) Avg. vascular age 15 yrs > chronologic age Thus: Increased Arterial Calcium Increased Risk Factor Profiles = Increased CAD Guaraldi G, et al. ClinInfDis 2009;49:1756-62

  36. Back to Our Case Risk for CVD in HIV most closely associated with age. Most important interventions: ART and smoking cessation. Jury out: statins, other lipid-lowering agents, ARV changes SMART Study NEJM 355:2293, 2006 DAD Study NEJM 356:1723, 2007

  37. Commonalities in Long-standing HIV Infection and the Normal Aging Process • Loss of Bone and Muscle Mass • Weight Gain / Loss • Decrease in GFR • Memory Loss • Immunosenescence • Frailty • Multi-Morbidity • Poly-pharmacy

  38. 100 Number of co-medications 80 0 60 % of participants 1 40 2 3 20 4+ 0 <50 years 50-64 years 65+ years Age Number of non-HIV meds by age B Haase CROI 2011

  39. Neurologic Issues in HIV and Aging • In patients enrolled in the Hawaii Aging HIV Cohort: • HIV-associated dementia 2x greater in subjects age ≥50 vs those age 20-39 (OR 2.13 [1.02-4.44]) • Increased Risk of HAD remains significant after adjustment for ART, HIV-1 RNA, CD4, education, race, drug use, and Beck Depression Inventory score (OR 3.26, [1.32-8.07]) Valcour Neurology 2004 Ances JID 2010

  40. Endocrinologic Morbidity • Testosterone Deficiency: 54% of HIV-infected patients had testosterone <300 ng/dL. • Low androgen levels were associated with increasing age, HIV+ IDU, HCV+ and use of psychotropic medications • Menopause: Occurs at younger age in HIV infection average age 46 (IQR 39-49) • Associated with increased symptoms of estrogen withdrawal Klein CID 2005; Schoenbaum E CID 2005

  41. BMD is lower and Fracture Prevalence is higher in HIV infection • BMD lower in HIV+ men at the femoral neck (p<.05) and lumbar spine ( p=0.06); • Differences significant after adjusting for age, weight, race, testosterone level, and prednisone and IDU • A 38% increase in fracture rate among HIV+ men Arnsten AIDS 2007 Triant J Clin Endo Metab 2008

  42. Psychosocial Issues • Isolation • Lack of support • Financial issues • DPOA / Directives

  43. Psychosocial Issues: Advance Care Planning • HIV, Aging, and Advance Care Planning • 238 HIV+ subjects [age 45-65]: • 47% had an Advance Directive • More likely with older, more educated subjects • J Palliative Med 15:1124-9, 2012 U Colorado

  44. Eras of the HIV Epidemic Chu and Selwyn, J Urban Health. 2011 Mar 1

  45. Things we need to study • High rates of comorbidities in older patients • Which ones are most important and to what extent are they due to age, HIV, and ART? • It is difficult to co-manage comorbidities and HIV together: • What’s the best timing of treating HIV and comorbid disease? Vis a vis Statins? Osteoporosis Rx? • Managing multi-morbidity and drug-drug interactions • We need to develop accurate treatment recommendations in older patients, or in the absence of this, best approaches • Problem: the cohort is growing but does not exist yet

  46. Conclusions • HIV / AIDS in US is increasingly an older population • Compared to younger patients, older HIV patients have: • Better virologic response, Less immunologic boost, Shortened survival • Comorbid disease is prevalent • Psychosocial issues and advanced directives are important, especially in the setting of multi-morbidity

  47. Principles • HIV: Early ART with attention to adherence, # meds • Aging: Comorbid disease / Multimorbidity / Frailty • HIV: Osteoporosis, Cancers, Cognition • Aging: Psychosocial Issues / Advanced Directives

  48. Recommendations • Start older patients with ART earlier for improved CD4 counts and reducing comorbidities • Watch closely for side effects/toxicities/polypharmacy • Screen for comorbid disease / multimorbidity • For osteoporosis • For cancer • For STD’s • Avoiding comorbid disease • Vaccinations • Smoking cessation, Exercise, Diet • Lipids, Hypertension, watch Creatinine Clearance • Treat Comorbid: • Substance Abuse /Mental Health • HCV • Address psychosocial issues and advanced directives

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