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Aging Gracefully with HIV

Aging Gracefully with HIV. Jonathan S. Appelbaum, MD, FACP, AAHIVS. Disclosure of Financial Relationships. This speaker has the following financial relationships with commercial entities to disclose: Salary/Contractual Services: Merck – Terminated

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Aging Gracefully with HIV

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  1. Aging Gracefully with HIV Jonathan S. Appelbaum, MD, FACP, AAHIVS

  2. Disclosure of Financial Relationships This speaker has the following financial relationships with commercial entities to disclose: • Salary/Contractual Services: Merck – Terminated This speaker will not discuss any off-label use or investigational product during the program. This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation.

  3. Objectives • Implement the newest screening and treatment guidelines for osteoporosis, hyperlipidemia and cancer screening as it pertains to HIV patients • Identify additional screening needs and proper treatment of HIV patients that are not recommended for the general population

  4. Case 1 • 95 yo AAF previously well presents with FTT and memory problems for the past several years • PMH: HTN, depression, h/o corneal transplant • Meds: HCTZ, fluoxetine • Soc: lives with daughter, husband died 1995. No Tobacco, ETOH, IDU

  5. On Exam • Thin woman (BMI 19) • Good skin turgor, no rashes • Edentulous, white plaque on posterior pharynx • No lymphadenopathy or palpable thyroid • Lungs and cardiac exam WNL • No abdominal masses, stool hemeneg • MMSE 24 • Neuro exam non-focal

  6. How would you prioritize this work up? • CBC/LFT’s/thyroid function tests • EGD/Colonoscopy • Chest/Abdomen/ Pelvic CT • HIV test • A first, then D, then B&C if needed

  7. The tests return….. • CMP, TSH normal • Mild normocytic normochromic anemia • EGD, colonoscopy negative • chest/abdomen/pelvic CT normal • HIV Ab+, CD4=141 VL=250K • Other Labs: RPR+ 1:8

  8. CDC Recommendations for HIV Testing (from MMWR, September 26, 2006, 55(RR 14); 1-17)

  9. Epidemiology • Increasing Prevalence • Prolonged survival due to HAART • New Infections

  10. Why are older patients getting infected?

  11. Why do you think that the number of older patients with HIV is increasing?

  12. Why are older patients getting infected? • Patient lack of awareness of HIV risk factors (sex and drugs) • Many older people are newly single • Belief that HIV only affects younger people • Unprotected sexual activity • Use of sildenafil and other ED drugs may contribute to increased rates of sexual activity • Menopause= No risk for pregnancy=No condom • No training in safer sexual activities • Lack of HIV prevention education targeted at older people • Seniors not considered at risk: don’t ask, don’t tell

  13. Sex is Not Only for the Young Proportion reporting sex in last 12 months LindauNEJM 2007 357(8):762-774

  14. Median CD4 count and the percentage of patients with a CD4 count ≥350 cells/mm3, at first presentation for HIV clinical care, by age <50yo: absolute increase in median CD4 = 67 cells/mm3 ≥50yo: absolute increase in median CD4 = 63 cells/mm3 Althoff, AIDS Res Therapy 2010

  15. Prevalence of AIDS, 12 Months after HIV Diagnosis by Age, 2007 HIV surveillance Report, Volume 20, CDC (2010)

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

  17. Mean Increase in CD4 by Age 2 years after ART Althoff K AIDS 2010

  18. What are older HIV-infected patients dying from? • PCP pneumonia • Wasting syndrome • Malignancy • Dementia

  19. The Changing Epidemic Among those initiating HAART(1996-2006) ART-CC. CID, 2010.

  20. HIV Outcomes with ART: What we Know Already

  21. Case #1-Follow-up • AZT/3TC/ABC/EFV: • Developed hallucinations • AZT/3TC/ABC/LPV/r: • Hepatitis • TDF/FTC/atazanavir: • Renal insufficiency • ABC/3TC/atazanavir: • Undetectable, CD4 400

  22. Recommendations When to Initiate Therapy • Antiretroviral therapy should be initiated in all patients older than 50 who have a CD4 count <500 cells/mm3 . • Antiretroviral therapy should be initiated in all patients older than 50, regardless of CD4 cell count, with the following conditions: AIDS-defining illness, HIV-associated nephropathy, or chronic hepatitis B virus infection. • For patients over age 50 who have a CD4 count >500 cells/mm3, antiretroviral therapy should be considered. Factors favoring initiating therapy include plasma HIV RNA levels greater than 50,000 copies/ml, greater than 100-point decline in CD4 count in prior 12 months, or risk factors for cardiovascular disease.

  23. Normal Aging Process • Loss of Bone and Muscle Mass • Weight Loss • Decrease in GFR • Memory Loss • Immunosenescence

  24. Treatment Issues in Older HIV Patients • Older people may have age-related losses of kidney and/or liver function which may change metabolism of drugs • Drug-drug interactions • Toxicities significant • Older people often excluded from many clinical trials and few subgroup analysis in older patients • Little pharmacokinetic data at extremes of age

  25. Case #2 • 63 yo AAF HIV x 10 yrs, CD4 420, VL <50 • PMH: HTN, depression, DM, hyperlipidemia • Meds: emtricitabine/tenofovir/efavirenz, HCTZ, citalopram, glargine insulin, lisinopril, EcASA, pravastatin • SH: lives alone, No tobacco,, IDU, has boyfriend and uses condoms intermittently • Difficulty with adherence to non-ART medicines • HbA1C >10, SBP >160

  26. 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

  27. 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 Bacterial pneumonia AIDS defining event Myocardial infarction Coronary angioplasty Pulmonary embolism Fracture, adequate trauma Fracture, inadequate trauma Procedures on other arteries Non AIDS defining malignancies Incidence of comorbidities: by age B Haase CROI 2011

  28. Potential Comorbidities Among Older Patients With HIV • Cardiovascular disease • Metabolic disorders • Diabetes • Dyslipidemias • Neurocognitive abnormalities • Liver and renal problems • Bone disorders • Osteopenia • Osteoporosis • Malignancies

  29. 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. ShielsAnnals of Int Med 2011

  30. Case #3 • 64 yo WM, HIV+ 22 years, no OIs. • Smokes 1 ppd x 40 yrs • Multiple ART, now on boosted darunavir, etravirine, raltegravir • CD4 321, HIV RNA <48 c/ml3 • Facial lipoatrophy, truncallipohypertrophy • Other meds: metformin, lisinopril, ASA • Reports decreased libido and ED

  31. To evaluate this patient’s concerns, he should have: • CBC/LFT’s/thyroid function tests • PSA • Free Testosterone • Total Testosterone • All of the above

  32. Endocrine • Testosterone Def: 54% 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 46 (IQR 39-49) • Associated with increased symptoms of estrogen withdrawal Klein CID 2005; Schoenbaum E CID 2005

  33. Which of the following recommendations should be your first counseling priority? • Diet? • Smoking? • Exercise? • BP control? • DM management?

  34. D:A:D Study: Is the Framingham Risk Estimation Valid in HIV-Infected Patients? Observed and predicted MI rates accordingto ART exposure (D:A:D Study n=23,468) 8 Incidence of MIs is low: 345 over 94,469 patient-years follow-up (3.7/1,000 patient-years) 7 Observed rates 6 5 Best estimate of predicted rates Rates per Thousand Patient-Years 4 3 2 1 0 3-4 4+ 2-3 <1 None 1-2 N=6805 N=10,574 N=5292 N=9050 N=8890 N=5973 n = ART exposure Duration of cART exposure (years) Law et al. HIV Med. 2006;7:218-230.

  35. Age per 5 years older Previous CVD Family history D:A:D Study: Risk Factors for CHD in an HIV+ Population Drug class: not sufficient # of events to examine yet Better Worse RR 1.17 (1.08-1.26) cART Therapy Male gender Smoking Diabetes mellitus (yes versus no) Hypertension (yes versus no) 0.1 0.5 1 5 10 Relative Rate of Myocardial Infarction (95% CI) Adjusted for BMI, HIV risk, cohort, calendar year and race Lundgren J,et al.12th CROI; 2005; Boston. Abstract 62. Copenhagen HIV Programme (D.A.D)

  36. Case #3—follow-up • Free/total testosterone decreased • PSA, CBC, LFTs normal • Started on testosterone replacement • Appropriate lab follow up done, no improvement in symptoms • Sildenafil added (dose-adjusted) with improvement

  37. Recommendations: Lipids • There is insufficient evidence to alter current recommendations for management of dyslipidemia or CVD/ cerebrovascular disease screening by specific age criteria. • Use Framingham Risk Score to guide decision.

  38. Case #4 • 77 yo WM HIV x 20 years, CD4 750, VL<50 • PMH: depression, HCV+ • Meds: tenofovir/emtricitabine, atazanavir with ritonavir • SH: lives alone, divorced, MSM, 2 children, 4 grandchildren; no tobacco/ IDU, rare ETOH

  39. Should this patient be screened for osteoporosis? • Yes • No • Don’t Know

  40. BMD Decreases With Age 30 Male Female 25 20 Change in Bone Volume (%) 15 10 Mean ±SE 40 50 60 70 Age (Years) Orwoll ES et al. Endocr Rev. 1995;16(1):87-116.

  41. Case #4 (con’t) • 77 yo WM HIV x 20 years, CD4 750, VL<50 • Meds: tenofovir/emtricitabine, atazanavir plus ritonavir • SH: lives alone, divorced, MSM, 2 children, 4 grandchildren; no tobacco/ IDU, rare ETOH • January 2011 Ice storm • Falls and breaks multiple bones

  42. BMD Lower and Fracture prevalence 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 ArnstenAIDS 2007 TriantJ Clin Endo Metab2008

  43. Recommendations: Osteoporosis Screening • Since older patients have bone loss due to osteoporosis, and since many HIV-infected patients on ART have accelerated bone loss, screening for (and aggressive treatment of) osteoporosis should be done • Since vitamin D deficiency is prevalent in older HIV-infected persons, screening for vitamin D deficiency is warranted

  44. Frailty • Frailty phenotype: 3 of 5 (weight loss, exhaustion, weakness, slowness, and low physical activity). • earlier occurrence in HIV-infected patients • Functional status – may be better indicator

  45. Frailty increases with age and time with HIV HIV-infected for 8-12 years at age 55  13.4% exhibit the frailty phenotype – 9-fold higher risk than age-matched controls Desquilbet, et al. J Gerontol Med Sci2007;62A:1279-86

  46. VACS Risk Index VACS - Veterans Aging Cohort Study Justice 2010 HIV Medicine

  47. Survival by VACS Risk Score(6 Years) Justice 2010 HIV Medicine

  48. Case 5 Presentation • 77 yo AAF HIV x 5 years, CD4 500, VL<50 • PMH: HTN, arrhythmia with AICD, depression, • Meds: tenofovir/emtricitabine/efavirenz, carvedilol, HCTZ, citalopram, pravastatin • SH: Caretaker for grandchildren, husband died 2008, No tobacco, ETOH, IDU • Family is unaware of diagnosis, impacts adherence to ART

  49. General Routine Health Maintenance • All Medications • Tobacco/ETOH/drug use • Nutrition • Injury Prevention: Burns/Falls/Driving • Bowel Habits/Incontinence • Psychosocial issues-$, end-of-life, social support and assisted living/SNF

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