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HIV and Aging 2012 HIV/STD/TB/Hepatitis Symposium Bismarck, North Dakota April 11, 2012

HIV and Aging 2012 HIV/STD/TB/Hepatitis Symposium Bismarck, North Dakota April 11, 2012. David McNamara, M.D. Infectious Disease Division Gundersen Lutheran La Crosse WI. Disclosures. None Dakota AIDS Education & Training Center. Learning Objective.

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HIV and Aging 2012 HIV/STD/TB/Hepatitis Symposium Bismarck, North Dakota April 11, 2012

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  1. HIV and Aging 2012 HIV/STD/TB/Hepatitis SymposiumBismarck, North Dakota April 11, 2012 David McNamara, M.D. Infectious Disease Division Gundersen Lutheran La Crosse WI

  2. Disclosures • None • Dakota AIDS Education & Training Center

  3. Learning Objective • At the end of the presentation, participants should be familiar with basics of: • Changes in age-related epidemiology among persons living with HIV • Links between HIV related inflammation and biology of aging • Age-related considerations for treating HIV in elderly persons

  4. What is Your Professional Discipline? • Nurse • Physician • Social Worker • Allied Health • Laboratory • Other

  5. Overview • Epidemiology • Biology of Aging and HIV • Treatment Considerations • Summary

  6. Why Is HIV and Aging Important? 1980s meets 2010s

  7. 1980s AIDS Crisis • HIV/AIDS primarily a disease of young and middle-aged men • 2010s • Convergence of HIV epidemic and aging of America • Consequence of medical success • Success in treatment of HIV • Success in non-HIV related treatments, Americans living longer

  8. Why the Intersection of Aging and HIV? • HIV in older adults due to: • Improved survival of persons with HIV • Acquisition of HIV among older persons • Likely more common than recognized • Likely ↑ mucosal risk of HIV acquisition in elderly

  9. cdc.gov

  10. http://www.cdc.gov/hiv/surveillance/resources/reports/2009report/index.htmhttp://www.cdc.gov/hiv/surveillance/resources/reports/2009report/index.htm • United States 2008: • Newly diagnosed persons with HIV • 16.5% > 50 years old • 30.5% persons living with HIV > 50 years old • By 2015, 50% people living with HIV will be > 50

  11. Improved Survival of Persons with HIV • 1990 to 2010 • patients age 50-64 in Swiss HIV Cohort: <3% to 25% • If trend continues, in 10 years ~50% of patients will be > 50 years old • Unimaginable outcome when AIDS first described in 1980s Hasse B et al. CID 2011;53: 1130.

  12. New diagnosis of HIV most common in 15-64 year old range • Significantly increased survival in persons with HIV in last 15 years • Large population of patients with HIV surviving to older age groups

  13. 44,491 HIV infected patients in US/Canada • 1997-2007: proportion of pts > 50 years old presenting for HIV care increased from 17% to 27% • Median CD4 count lower in > 50 year olds than younger pts • AIDS diagnosis at or within 3 months of presentation • <50 years old: 10% • >50 years old 13% Althoff et al. AIDS Research and Therapy 2010 7:45.

  14. Why Older Persons Acquire STIs (including HIV) • Lack of awareness of HIV risk factors • Newly single • Increased ease in finding new partners • Menopause • No pregnancy risk, little condom use • Increased vaginal mucosal trauma/risk • Unprotected intercourse: less condom use ? • Viagra: increased sex among elderly • Lack of HIV prevention services for older persons • Healthcare providers don’t consider seniors at risk • “Don’t ask, don’t tell”

  15. Sex Not Only for the Young • Limited information on sexual behavior in older adults and how sexual activities change with aging and illness • Large market for medications/devices to treat sexual problems targets older adults • National sample of 1550 women, 1455 men ages 57-85 • Response rate 75% Lindau ST. NEJM 2007; 357:762.

  16. Older adults often sexually active • Prevalence of sexual activity declined with age • Women less likely than men to report sexual activity • 14% men took medication to aid sexual activity • Poor health associated with decreased sexual activity, sexual problems Lindau ST. NEJM 2007; 357:762.

  17. Implications for HIV Care Workforce • Needs of patients with HIV are changing due to • advances in Antiretroviral Therapy (ART) • improved survival of patients

  18. What is your role in HIV Care? Nursing Public Health Nurse Physician NP or PA I don’t provide direct patient care

  19. When did you first meet patients with HIV? • 1980s • 1990s • 2000s • 2010s

  20. HIV Care in U.S. • 1980s: AIDS Crisis emerges • Oncology, ID, IM, Peds, FP • Sense of mission, addressing emerging AIDS crisis • Diagnosis, treatment and end-of-life care • AIDS-related diseases, often no effective treatment • Most primary care providers avoided HIV care • Complexity, rapid changes in HIV treatment • Sometimes discomfort/antipathy towards patients with HIV and their lifestyles • 1995-2000s: HIV became a treatable chronic infection • ID specialists, fewer IM/FP involved in HIV care • Antiretroviral therapy → remarkably improved survival • Complexity and speed of development of ART • HIV Care not in mainstream of primary care Saag M. CID 2011; 53:1140.

  21. Future HIV Care Workforce • 60-75% HIV patients in community practices have well-suppressed HIV viral loads • Care of aging HIV patients requires: • HIV-specific expertise • Primary care skills and organization • Address non-HIV aspects of aging • Often accelerated by HIV infection • Ryan White clinics outstanding models of “medical homes” with access to medical, nursing, mental health and social services • Future? • Increasing need for integration of Primary Care into HIV Clinic • ID specialists improve primary care skills, knowledge or refer patients to IM/FP for ongoing primary care • New HIV specialists/clinics emerging • Primary Care providers with interest/training in HIV Care • ID specialists with a focus on outpatient HIV Care • Often multidisciplinary clinics with mid-level providers Saag M. CID 2011; 53:1140.

  22. Overview • Epidemiology • Biology of Aging and HIV • Treatment Considerations • Summary

  23. Aging • Progressive deterioration in physiologic function that accrues as a consequence of cumulative molecular, cellular and organ damage • Impaired ability to maintain physiologic equilibrium with stress • These changes invariably result in increased susceptibility to death

  24. Evolution and Aging • “Nothing in biology makes sense except in light of evolution” • Aging results from greater weight placed by natural selection on early survival and reproduction than on vigor at later ages • Natural selection favors gene variants that promote early growth and reproduction • Genes that ensure a powerful immune response to infection promote early life survival, but later contribute to inflammation, a major age-related phenotype and risk for developing many diseases Vijg and Campisi. Nature 2008; 454: 1065

  25. Normal Aging • Loss of bone and muscle mass • Weight loss • Decline in kidney function • Memory loss • Immunosenescence • ↑ risk of Herpes zoster, UTI, bacterial infections, cancers • Lymphopenia, decline in CD4 cell count • “Inflamm-aging” • ↑ Proinflammatory cytokines, systemic low grade inflammation

  26. Frailty Geriatric syndrome weakness weight loss slow walking speed low activity subjective feeling of exhaustion Strongly associated with adverse health outcomes in elderly Assumed to be a physiologic consequence of multiple co-morbid conditions, resulting in biologic vulnerability, lack of ability to compensate for stresses Similar to wasting seen in HIV infection HIV patient: “I feel less healthy than my father!”

  27. Does HIV or its Treatment Accelerate the Aging Process? • Epidemiologic Data • Does HIV alter the biology of aging?

  28. HIV and Clinical Manifestations of Accelerated Aging • Since 1995 and introduction of ART, primary causes of illness/death: •  AIDS-related illnesses • ↑ chronic non-communicable conditions typically associated with aging • Many age-associated diseases more common in treated HIV disease than in age-matched HIV negative persons • Cardiovascular disease • Non-AIDS cancers • Osteopenia, bone fractures • Liver and renal failure

  29. 8444 patients in Swiss HIV Cohort Study • 2008-2010 • Median • age 45 years old • nadir CD4 190 cells/uL • current CD4 528 cells/uL • 70% male • 23% prior AIDS diagnosis • 69% undetectable HIV viral load Hasse B et al. CID 2011;53: 1130.

  30. During follow up, in this cohort: • 195 AIDS related events • 994 non-AIDS events • 39 strokes • 55 Myocardial infarctions • 70 diabetes diagnoses • 115 non-AIDS malignancies • 160 fractures • Non-AIDS conditions more common after age 50 • “..non-AIDS diseases, particularly diabetes mellitus, cardiovascular disease, non-AIDS defining malignancies, and osteoporosis, become more important in care of HIV-infected persons and increases with older age.” Hasse B et al. CID 2011;53: 1130.

  31. Implications • Hasse et al study did not address relative frequency of conditions in HIV vs. non-HIV patients • Reveals remarkable success of modern treatment era of AIDS care • Raises question: what’s next? Saag M. CID 2011; 53:1140.

  32. Guaraldi G et al. CID 2011; 53:1120 • Prevalence of non-infectious co-morbidities among patients on ART versus HIV negative controls? • Cross sectional retrospective case control study • 2854 HIV infected patients in Italy • Mean age 46 • Median • duration HIV infection 16 years • Nadir CD4 170 cells/uL • Current CD4 520 cells/uL • 8562 age, sex matched HIV neg. controls

  33. HIV+ patients at all ages: • ↑ prevalence of renal failure, bone fracture, diabetes, > 2 conditions simultaneously • < 60 years old, HIV patients ↑ prevalence of CV disease, HTN than HIV neg controls Guaraldi G et al. CID 2011; 53:1120

  34. HIV patients developed polypathology earlier than controls • Associated with ↑ age, male gender, nadir CD4 <200, lipoatrophy, lipodystrophy • Polypathology risk: 40 year old HIV+ similar to 55 year old HIV neg control Guaraldi G et al. CID 2011; 53:1120

  35. Capeau J. CID 2011;53. • Patients with well controlled HIV infection age more rapidly, die earlier than HIV negative controls • HIV patients accumulate age related diseases, polypathology more rapidly than HIV negative controls

  36. Does HIV or its treatment Accelerate the Aging Process? Epidemiologic Data Does HIV alter the biology of aging?

  37. Desquilbet L. J AIDS 2009; 50(3): 299 • Prior research (Desquilbet J 2007) showed frailty risk in HIV+ patients similar to HIV neg persons 10 years older • FRP evaluated in 1046 men in MACS study 1994-2005 • Prevalence of FRP low with CD4 > 400 cells/uL • FRP associated exponentially with low CD4 cell count • “CD4 T-cell count predicted the development of a frailty-related phenotype among HIV infected men, independent of HAART use. This suggests that compromise of the immune system in HIV-infected individuals contributes to the systemic physiologic dysfunction of frailty.”

  38. Why do HIV+ patients seem to have evidence of premature aging? • ↑ Prevalence of risk factors in HIV+ patients? • Treatment toxicities? • Effect of HIV infection itself?

  39. Higher Incidence of Usual Risk Factors vs. Effect of ART? • Traditional risk factors are major predictors of MI • Age, gender, DM, HTN, ↑cholesterol • DAD study provided insight into ART toxicities • PIs ↑ vascular risk than NNRTIs DAD Study, NEJM 2007; 356:17.

  40. DAD Study, NEJM 2007; 356:17. • Treatment toxicities • Cumulative exposure to PIs independently increased risk of MI • Increased lipids • Other, unexplained risks? • Abacavir ↑ CAD risk • Tenofovir: ↑renal failure risk

  41. Does HIV or its treatment Accelerate the Aging Process? Epidemiologic Data Does HIV alter the biology of aging? Hypothesis: Persistent immune activation in HIV+ patients → inflammation ↓ • Increased risk of non-AIDS related complications and premature aging

  42. Pathogenesis of HIV and Aging share some similarities on cellular and organ basis • Common link may be inflammation

  43. Pathogenesis of HIV • Massive depletion of CD4+ T cells • Paradoxical immune activation • Anti-HIV, CMV responses • ↑ Translocation of bacterial products across gut • ↑ Pro-inflammatory cytokines • Exhaustion of immune resources • Cellular turnover, senescence, apoptosis • Accumulation of aging T cells • Loss of regenerative capacity • Hypothesis: HIV infection induces accelerated process of immunoscence and systemic aging Immune activation and inflammation in HIV-1 infection: causes and consequences. Appay V. J Pathology 2008; 214(2)

  44. Appay V. J Pathology 2008; 214(2)

  45. Overview • Epidemiology • Biology of Aging and HIV • Treatment Considerations • Summary

  46. Age of oldest patient with HIV you have cared for/personally known? 40s 50s 60s 70s 80+

  47. Diagnostic Issues • Diagnosis of HIV often delayed in elderly • Manifestations of HIV/AIDS often present similar to other geriatric syndromes • Delirium • Dementia • Failure to Thrive: wasting, weight loss, frailty • Bacterial infections • Pneumonia • Cytopenias • Obtain an HIV Ab when evaluating elderly persons for above geriatric syndromes • Inexpensive, easy, important to rule out or identify if present

  48. Antiretroviral Treatment Issues in Older HIV Patients • Decreased kidney and liver function • Changes metabolism of drugs • Drug-drug interactions • Toxicities significant • Older persons often excluded from clinical trials • Little pharmacokinetic data in children and elderly

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