The Graying of the HIV/AIDS Epidemic in the U.S.

2. The Graying of the HIV/AIDS Epidemic in the U.S.

3. Effects of Aging on the Course of HIV Infection- and Vice Versa - James R. Minor, Pharm.D CAPT, USPHS, Retired jminor101422@gmail.com 919-641-2856 June 2012

4. Disclaimer

5. Objectives • Describe the clinical issues affecting older HIV+ patients • Describe ‘immunosenescence’ and its impact on the course of HIV infection in older patients • Summarize HIV-associated, non-AIDS conditions and co-morbidities

6. HIV/AIDS in Older Persons[50 years of age or older]

7. The Numbers [US] Persons 50 years of age+ account for: • 15% of all new HIV infections/year • 20% of all new AIDS diagnoses • 35% of all deaths due to AIDS • 25% of persons living with AIDS [up from 17% in 2001]

9. Common AIDS and Non-AIDS Complications

10. HIV+ persons have a substantially shortened life span, largely due to increased risks of ‘non-AIDS’ complications and comorbid diseases : renal, bone, metabolic, liver, malignant diseases, and neurocognitive decline

11. Risk of non-AIDS morbidity is higher among ARV-treated HIV+ individuals than in their age-matched, uninfected peers for reasons directly related to the disease or its treatment

12. All these degenerative comorbid diseases have a negative impact on overall functioning and Quality of Life, and are thought to be related to accelerated or premature aging

13. ‘Immunosenescence’

14. ‘Immunosenescence’- Definition - • Age-related changes in the adaptive immune system that are associated with increased morbidity and mortality

15. ‘Immunosenescence’ Adaptive immune system changes with aging: • Decreased number and function of hematopoietic stem cells • Thymic dysfunction, involution • Decreased circulating naïve T cells • Decreased CD4/CD8 ratios • Increased proinflammatory cytokines: IL-6, TNFα, CRP, cystatin C • Increased pools of senescent CD28- ‘memory’ cells *

16. Senescent T Cells • With aging or in the presence of chronic viral infection, CD28- T cells become resistant to apoptosis and become pro-inflammatory in effector function • This contributes to increased systemic inflammationand collateral harm to multiple organ systems

17. HIV-associated inflammation and ‘immunosenescence’ have been implicated as causally related to the premature onset of multiple end-organ diseases

18. ‘Immunosenescence’ - Summary - • HIV-associated immunosenescence contributes to persistent immunodeficiency and early onset of age-related diseases • Further investigation into these pathways may lead to novel therapeutic interventions useful in both HIV-infected persons and in uninfected geriatric populations

20. Prevention and Public Health Challenges in Older HIV+ Persons • Many older persons are sexually active but may not be practicing safer sex • Older women are at higher risk due to age-related genital changes • Many older persons may know less about HIV/AIDS and less likely to protect themselves or to get tested • Discrimination and stigma facing older HIV+ may delay testing, diagnosis and entry in treatment

22. HIV and Aging: Overall Framework

23. Renal Disease

25. Renal Disease • Untreated HIV disease [persistent viral replication] is associated with higher risks of kidney disease – suggesting that HIV replication directly or indirectly affects the kidneys • Many antiretroviral agents [ARVs] are also nephrotoxic

26. Bone Disease

28. Bone Disease • Prevalence of osteopenia and osteoporosis is at least 3x greater in HIV+ subjects than in HIV uninfected controls • Persistent inflammation is probably causally related to bone disease, as many biomarkers of inflammatory bone disease are higher in HIV disease [IL-6, TNF… ] • Other contributory factors: ART, vitamin D deficiency

30. Metabolic and Cardiovascular Complications

36. HIV, Aging and Increased Risks ofMalignant Diseases

37. Non-AIDS Related Cancers • Higher cancer rates in long-term ARV-treated patients is strongly related to the degree of immunodeficiency • HIV-associated immune deficiency may be the primary factor driving an excess risk of many non-AIDS cancers • Increasing prevalence 0f HCV- and HPV- related malignancies

39. Kaposi’s Sarcoma

40. Neurocognitive Functional Defects

42. HIV-Associated Neurocognitive Disorders [HAND] and Dementia [HAD]:A Hidden Epidemic ??

43. Neurocognitive Decline • HIV-associated inflammation is believed to be a major factor in comorbid CNS disease • Debate: Is ongoing CNS disease due to inadequate CNS penetration of ARVs [allowing ongoing viral replication] OR to residual, low-grade inflammation ??

44. HIV and Aging: Overall Framework

46. The ‘double insult’ of aging and HIV infection to the hematopoietic system can contribute to many of the factors associated with immunosenescence: chronic inflammation, reduced ability of the immune system to mount effective response to infections, vaccines, other stressors

47. Novel therapeutic strategies aimed at preventing or reversing immunologic defects and changes related to immunosenescence will be necessary if HIV-infected patients are to achieve normal life spans