HIV & Aging: Evolving Clinical Considerations in the New Millennium

Transcription

1 HIV & Aging: Evolving Clinical Considerations in the New Millennium Julian Falutz, MD, FRCP (C) Director, HIV Metabolic Clinic Immunodeficiency Treatment Centre Senior Physician Division of Geriatrics McGill University Health Centre March 2010

2 Goals Review principles of HIV management and outcome characteristics Discuss changing epidemiology of HIV in older subjects Discuss changing spectrum of clinical conditions and possible pathophysiologic contributors

3 Principles of HIV management

4 AIDS-related mortality Weiss RA. Nat Med 9(7), 2003

5 HIV Life Cycle

6 Inhibition of HIV replication (4) (1) (2) (3) Fauci AS. Nat Ned 9(7), 2003

7 Currently approved antiretroviral drugs Entry inhibitors Reverse transcriptase inhibitors Protease inhibitors Integrase inhibitors Nucleoside Nucleotide Nonnucleoside Single compound tablets Enfuvirtide (T-20) Maraviroc Abacavir Didanosine Emtricitabine Tenofovir Delaviridine Efavirenz Nevirapine (Fos)-Amprenavir Atazanavir Darunavir Raltegravir Lamivudine Etravirine Indinavir Stavudine Nelfinavir Zalcitabine Ritonavir Zidovudine Saquinavir Tripanavir Lopinavir/ritonavir Fixed dose combination tablets Zidovudine/lamivudine Tenofovir/emtricitabine Abacavir/lamivudine Tenofovir/emtricitabine/efavirenz Adapted and updated from Simon V et al. Lancet 2006;368:

8 Changing survival

9 Mortality and HAART Over Time

10 Survival of treated HIV patients 60 Age at diagnosis Age 20 Age Stratified by treatment period Stratified by baseline CD Lancet 2008;372: < >200

11 Possible equivalent mortality rates to controls in some HIV+ adults on effective long-term HAART standardized mortality ratios SMRs Lewden C et al. JAIDS 2007;46(1):72-7

12 Changing Demographics

13 Older HIV Patients Successfully treated chronically infected patients New seroconverters

14 Age distribution (in yrs) of HIV-infected individuals living in the United States 15% HIV+ >50 yo in 2005: anticipated 50% >50 yo in 2015 Effros RB et al. CID 2008;47:542-53

15 Increasing prevalence of HIV+ adults > 55 yo regardless of mode of HIV transmission HIV & Ageing, Krakow 2008 (hivtri.com)

16 Increasing age of HIV seroconverters Source: CASCADE Collaboration

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18 Age-related treatment response characteristics

19 HIV RNA and CD4 cells at baseline and after HAART in patients <50 yrs old> Median log 10 (HIV- RNA) evolution! Median CD4 + T cell count/mm 3 evolution Nogueras M et al. BMC Inf Dis 2006;6:159

20 Baseline CD4 counts predicts the % of patients achieving (near) normal CD4 counts in response to HAART Kelley CF et al. Clin Inf Dis 2009;48:787-94

21 Summary Virologic and immunologic responses to HAART in older vs younger persons -similar or better HIV reduction in HIV viral load -possibly lower nadir CD4 count -smaller increase in CD4 counts in response to HHART -durability of responses unknown -risk of AIDS or non-aids events related to both lower nadir CD4 s and lower maximal CD4 plateau

22 But, success comes at the price of unexpected consequences

23 Changing causes of mortality: decrease in AIDS-related but increase in serious non- AIDS-related events (SNARE) Pre-HAART Early HAART Current HAART 0 AIDSdefining HIV-related non-aids defining Non-HIV related Crum NF et al. JAIDS 2006; 41(2):

24 Proportion of AIDS and non-aids events by latest CD4+ count Baker JV et al. AIDS 2008;22:841-48

25 Increased mortality risk associated with nonfatal AIDS and serious non-aidsrelated events (SNARE) p = 0.09 Neuhaus J et al. AIDS 2010;24:000

26 Psycho-social CVD Function Frailty Cognition Liver Aging & HIV Cancer Kidney Bone

27 Current HIV admissions at MGH Sex Age Diagnosis HAART CD4 VL M 54 Acute renal failure Yes M 60 Pancreatic CA Yes M 46 Renal cell CA Yes M 65 Myocardial infarction Yes M 50 Trauma No 324 4,010 M 33 CNS toxo No ,302 M 46 R/O lymphoma No 83 na F 47 Brain lesion No 200 na

28 HIV, Ageing & Metabolic Complications

29 HIV/HAART Associated Metabolic Abnormalities Peripheral fat loss Dyslipidemia Lactic Acidemia Central fat gain Glucose Homeostasis Abnormality Bone Demineralisation

30 HIV, Ageing & CVD Risks

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32 Increased rates of acute MI and CV risks among HIV+ patients Triant VA et al. JCEM 2007;92(7):

33 HIV, Ageing & Bone

34 SUN Study: prevalence of osteopenia/osteoporosis in HIV-infected patients Comparison of Femoral Neck T-Scores Among SUN Study Participants and Matched Controls Proportion SUN study participants Matched NHANES subjects Mean: Mean: P <.001 Multivariate Analysis: Factors Related to Osteoporosis Factor OR (95% CI) P Value BMI < 22.5 kg/m² 3.01 ( ) <.001 Age > 45 years 2.35 ( ).003 BL CD4+ < ( ).013 HIV > 97.7 mos 1.56 ( ) T-Score Overton T et al. CROI Abstract 836.

35 MGH HIV Clinic (n=135 males) Total hip Lumbar Spine Normal (31%) Osteopenia (44%) Normal (41%) Osteopenia (53%) Osteoporosis (25%) Osteoporosis (6%) Falutz J.

36 Fracture prevalence in HIV patients p = 0.09 Triant VA et al. JCEM 2008;93(9):

37 HIV & Cancer

38 Changing cancer incidence rates by HAART availability periods Crum-Cianflone N et al. AIDS 2009;23:41-50

39 Incidence of non-aids-defining malignancies in HIV-infected vs non-infected patients in the HAART era p = 0.09 Bedimo RJ et al. JAIDS 2009;52(2):203-8

40 Incidence of non-aids cancers in HIVinfected individuals p = 0.09 Shiels MS et al. JAIDS 2009;52(5):611-22

41 HIV, Ageing & Cognition

42 Neurocognitive impairment The age-specific prevalence of dementia almost doubles every 5 years, from approximately 1.5% in persons aged years to 40% in persons older than 85 Qui et al. Curr Opin Psychiatry 2007;20:380-5

43 Possible risk factors for cognitive decline in stable, community dwelling middle-age & elderly subjects Insulin resistance Type II diabetes mellitus (systolic) hypertension Abdominal obesity Inadequate sleep + sleep apnea Lack of physical activity Low HDL * * * Limited social networks * * * * * * present in HIV + adults

44 Decreased prevalence of HIV-associated dementia (HAD) in treated HIV+ subjects Larussa D et al. AIDS Res & Hum Retroviruses 2006;22(5):386-92

45 Persisting (increasing?) proportion of HIV+ patients with non-dementia neurocognitive impairment NC = normal cognition ANI = asymptomatic neurocognitive impairment MND = mild neurocognitive disorder HAD = HIV-associated dementia Dulioust A et al. CROI 09

46 Correlation between composite neuropsychologic score (NPZ8*), CD4 cells and age, but no correlation between HIV-RNA and NPZ8 Age CD4 HIV-RNA p = p = p = 0.09 p = *NPZ8 an average of individual scores for 8 neuropsychologic tests Giancola ML et al. JAIDS 2006;41(3):332-37

47 HIV, Ageing & Frailty

48 Frailty as a geriatric syndrome Common biologic syndrome in the elderly (25-40% of >80 y.o.) Characteristics include: - loss of appetite - loss of lean body mass - bone demineralization - fatigue - risk of falls - overall poor health Increases vulnerability to adverse health outcomes including disabilities, dependency, long-term care, death Arises from declines in molecular, cellular and physiologic systems of the aged body Reduces stress tolerance because of decreased reserves in muscles, bones, circulation, hormone & immune systems

49 Objective definition of frailty* as proposed by Fried et al Morley JE et al. The Aging Male 2005;8(3/4):135-40

50 HIV-1 is associated with an earlier occurrence of the Frailty Related Phenotype (FRP) OR for HIV+ vs HIV- men to manifest each of the 4 components of the FRP and the overall FRP Frailty Component Physical shrinking Exhaustion Slowness Low physical activity level Overall FRP OR OR OR OR OR PV* analyzed PV without weight loss *PV = patient visits Desquilbet L et al. J Gerontol 2007;62A(11):

51 Clinical Significance The number of HIV-infected adults over the age of 50 yrs is increasing Larger numbers of older adults are diagnosed with new HIV infection The majority of older HIV patients aged into this category, as therapy substantially increased life expectancy The complexities of caring for older HIV-infected patients are largely un-investigated Diagnosis of HIV in older adults is often delayed and treatment is complicated by side effects and drug interactions Martin CP et al. Am J Med 2008;121:

52 Providing care for the older HIV+ patient is going to be very complicated Physical and Medical Challenges Aging Co-morbidities Polypharmacy Social and Psychological Factors Patients are often isolated and tend to live alone Stigma Mental health and behavioural health Higher rates of depression Substance use alcohol and drugs Services and Support Difficulties of accessing services geared to the non-hiv Homophobia and HIV phobia among elderly service providers and individuals

53 Thank you