1. 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

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

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

4. What is Your Professional Discipline? 1. Nurse 2. Physician 3. Social Worker 4. Allied Health 5. Laboratory 6. Other

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

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

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

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

10. cdc.gov

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

12. 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.

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

15. 44,491 HIV infected patients in US/Canada 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% 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 Median CD4 count lower in > 50 year olds than younger pts AIDS diagnosis at or within 3 months of presentation AIDS diagnosis at or within 3 months of presentation <50 years old: 10% <50 years old: 10% >50 years old 13% >50 years old 13% Althoff et al. AIDS Research and Therapy 2010 7:45.

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

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

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

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

20. What is your role in HIV Care? 1. Nursing 2. Public Health Nurse 3. Physician 4. NP or PA 5. I don’t provide direct patient care

21. When did you first meet patients with HIV? 1. 1980s 2. 1990s 3. 2000s 4. 2010s

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

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

24. Overview Epidemiology Epidemiology Biology of Aging and HIV Biology of Aging and HIV Treatment Considerations Treatment Considerations Summary Summary

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

26. Evolution and Aging “Nothing in biology makes sense except in light of evolution” “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 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 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 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

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

28. Frailty Geriatric syndrome Geriatric syndrome weakness weakness weight loss weight loss slow walking speed slow walking speed low activity low activity subjective feeling of exhaustion subjective feeling of exhaustion Strongly associated with adverse health outcomes in elderly 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 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 Similar to wasting seen in HIV infection HIV patient: “I feel less healthy than my father!” HIV patient: “I feel less healthy than my father!”

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

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

31. 8444 patients in Swiss HIV Cohort Study 8444 patients in Swiss HIV Cohort Study 2008-2010 2008-2010 Median Median age 45 years old age 45 years old nadir CD4 190 cells/uL nadir CD4 190 cells/uL current CD4 528 cells/uL current CD4 528 cells/uL 70% male 70% male 23% prior AIDS diagnosis 23% prior AIDS diagnosis 69% undetectable HIV viral load 69% undetectable HIV viral load Hasse B et al. CID 2011;53: 1130.

32. During follow up, in this cohort: During follow up, in this cohort: 195 AIDS related events 195 AIDS related events 994 non-AIDS events 994 non-AIDS events 39 strokes 39 strokes 55 Myocardial infarctions 55 Myocardial infarctions 70 diabetes diagnoses 70 diabetes diagnoses 115 non-AIDS malignancies 115 non-AIDS malignancies 160 fractures 160 fractures Non-AIDS conditions more common after age 50 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.” “..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.

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

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

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

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

37. 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

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

39. 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 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 FRP evaluated in 1046 men in MACS study 1994-2005 Prevalence of FRP low with CD4 > 400 cells/uL Prevalence of FRP low with CD4 > 400 cells/uL FRP associated exponentially with low CD4 cell count 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.” “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.”

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

41. 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.

42. Treatment toxicities Cumulative exposure to PIs independently increased risk of MI Increased lipids Other, unexplained risks? Abacavir ↑ CAD risk Tenofovir: ↑renal failure risk

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

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

45. 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)

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

47. Overview Epidemiology Epidemiology Biology of Aging and HIV Biology of Aging and HIV Treatment Considerations Treatment Considerations Summary Summary

48. Age of oldest patient with HIV you have cared for/personally known? 1. 40s 2. 50s 3. 60s 4. 70s 5. 80+

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

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

51. Number of Non-HIV Medications by Age Patients often taking > 5 medications Patients often taking > 5 medications Increased comorbidities with age Increased comorbidities with age Hasse B et al. CID 2011;53: 1130

52. Benefit of starting ART early in elderly? Elderly often have lower CD4 counts on presentation Elderly often have lower CD4 counts on presentation May benefit from starting ART even when CD4 > 500 cells/uL May benefit from starting ART even when CD4 > 500 cells/uL Attempt to decrease risk of frailty associated with low CD4 counts Attempt to decrease risk of frailty associated with low CD4 counts

53. Psychosocial Issues Often unique to HIV+ elderly, different than Often unique to HIV+ elderly, different than Younger patients with HIV Younger patients with HIV HIV negative elderly HIV negative elderly Common concerns Common concerns Disclosure Disclosure Peers, church, neighbors, family of HIV+ seniors often less familiar/ comfortable with HIV than peers of younger patients Peers, church, neighbors, family of HIV+ seniors often less familiar/ comfortable with HIV than peers of younger patients Isolation Isolation Lack of social support Lack of social support Financial issues Financial issues ART expense, Medicare Part D coverage ART expense, Medicare Part D coverage End of Life suffering, support End of Life suffering, support

54. Other Important Issues Common competencies of Geriatricians, less familiar to ID/HIV specialists: Common competencies of Geriatricians, less familiar to ID/HIV specialists: Sexuality in elderly Sexuality in elderly Mobility Mobility Mentation/Depression/Dementia Mentation/Depression/Dementia Hearing/vision impairment Hearing/vision impairment Activities of Daily Living Activities of Daily Living What can patient do for themselves in their home environment? What can patient do for themselves in their home environment?

55. Overview Epidemiology Epidemiology Biology of Aging and HIV Biology of Aging and HIV Treatment Considerations Treatment Considerations Summary Summary

56. Epidemiology Epidemiology Prevalence of HIV increasing among elderly Prevalence of HIV increasing among elderly HIV patients living longer, aging HIV patients living longer, aging Biology Biology HIV patients age more rapidly than HIV negative controls HIV and aging may share link with chronic inflammation HIV and aging may share link with chronic inflammation Treatment Considerations Treatment Considerations Consider starting older patients on ART earlier Consider starting older patients on ART earlier Attention to co-morbidities, vascular disease important Attention to co-morbidities, vascular disease important

57. Acknowledgements Acknowledgements Anne Grande, Education Coordinator Dakota AIDS Education & Training Center Anne Grande, Education Coordinator Dakota AIDS Education & Training Center Drs. Kelly Gebo and Steve Deeks Drs. Kelly Gebo and Steve Deeks HIV and Aging, IDSA 2011 Boston HIV and Aging, IDSA 2011 Boston Further resources: Further resources: cdc.gov cdc.gov North Dakota Department of Health, North Dakota Department of Health, www.ndhealth.gov www.ndhealth.gov

58. Public Health Image Library, cdc.gov