HIV and the Aging Patient: Managing Co-morbidities. Heather Free, PharmD, AAHIVP

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HIV and the Aging Patient: Managing Co-morbidities Heather Free, PharmD, AAHIVP

Objectives Review HIV/AIDS statistics within the United States Define HIV and Aging and life expectancy List treatment issues that are of greater concern in older people with HIV Discuss factors that make DDI more complicated in older people with HIV Disclosure: I will not discuss non-fda approved or investigational uses of any products/devices

Understanding HIV Where You Live

AIDSVu vs. CDC Stats

Persons Living with Diagnosed or Undiagnosed HIV Infection HIV Continuum Outcomes by Race/Ethnicity, 2014 United States

Persons Living with Diagnosed or Undiagnosed HIV Infection HIV Continuum Outcomes by Transmission Category, 2014 United States

Global HIV Response World Health Organization 2000-2015

HIV Trends per Our World in Data

Early HAART Regimens Were No Fun Morning Afternoon Evening # Pills AZT 6 3TC 2 X3 X3 X3 NFV 9 Total HAART 17 Side Effects: 25 pills daily! 3 tablets/day 5 tablets/day

Growing Older with HIV HIV and Aging: what does this mean for the medication cocktail?

HIV and Aging More and more HIV patients are living longer Aging process is more accelerated in an HIV+ patient vs HIVdue to increased inflammation Classified at 50 YO Virally suppressed HIV+ patients are more prone to death from non-aids co-morbidities Wing, Edward J. HIV and aging. International Journal of Infectious Disease 53 (2006) 61-68.

AGEhIV: Older HIV-Infected Patients at Increased Risk for Multiple Co-Morbidities Cross-sectional analysis of co-morbidity prevalence in prospective cohort study of HIV-Infected patients (n=540) vs controls (n=524) 45 YO Schouten J, et al. The AGEnIV Cohort Study. Clin Infect Dis. 2014;59:1787-1797.

AGEhIV Comorbidities Schouten J, et al. The AGEnIV Cohort Study. Clin Infect Dis. 2014;59:1787-1797.

Factors Related to Non-AIDS Co-morbidities in HIV-Infected Patients AGING Chronic HIV infection HCV and other coinfections Genetics Obesity, exercise, diet, smoking Stress Depression Inflammation and fibrosis Dyslipidemia Insulin resistance Decreased physical functioning Cardiovascular Renal Metabolic Functional Neuropsychiatric Warriner AH, et al. Infect Dis Clin North Am. 2014; 28:457-476.

HIV and Inflammation Hypothesis: HIV infection induces a persistent inflammatory response, resulting in pathogenic responses and end-organ disease Elevated levels of inflammatory markers associated with increased risk of non-aids co-morbidities and mortality in HIV-infected patients ART partially reduces some inflammatory biomarker levels 1. Tenorio AR, et al. J Infect Dis. 2014;210:1248-1259 2. So-Armah KA, et al. J Acquir Immune Defic Syndr. 2016;72:206-213.

Inflammation Associated with Disease in Treated HIV Infection Mortality Cardiovascular Disease* Cancer Venous Thromboembolism Type 2 Diabetes Renal Disease Cognitive Dysfunction Depression Functional impairment/frailty* 1. Tenorio AR, et al. J Infect Dis. 2014;210:1248-1259 2. So-Armah KA, et al. J Acquir Immune Defic Syndr. 2016;72:206-213.

Cardiovascular Disease and HIV HIV+ patients are at increased risk for cardiovascular disease (CVD), including myocardial infarction (MI) and stroke. Patients with HIV should undergo screening for CV risk using the ACC/AHA risk calculator Prevention to lower risk of CVD include: Diet Exercise Smoking cessation Evaluation of lipid-lowering agents (Smart 2006, McComsey 2012, Torriani 2008)

Screening and Assessing Cardiovascular Risk 10 Year ASCVD Risk: Pooled Cohort Equation Demographics Age (40-79 year), gender and race History HTN, DM, tobacco use Measurements Total Cholesterol, HDL, systolic blood pressure Goff Jr Et Al. 2013 ACC/AHA guidelines on the assessment of cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol.2014; 63:2935-2959.

ACC/AHA Statin Benefit, Adapted from Stone NJ et al. 2013 report on the treatment of blood cholesterol to reduce ASCVD in adults. Circulation. 2014; 129:S1-S45. Yes No Yes No Yes No Yes

Statin Selection +ART PI- or COBI-Containing Regimens High-Intensity Statins Moderate-Intensity Statins Low-Intensity Statins Atorvastatin 20mg Atorvastatin 10mg Pravastatin 10-20mg Rosuvastatin 10-20mg Rosuvastating 5mg Fluvastatin 20-40mg Pravastatin 40-80mg* Pitavastatin 1mg Pitavastatin 2-4mg Simvastatin and lovastatin are contraindicated for patients receiving a PI, COBI, and/or RTV *With darunavir, reduce pravastatin to 20-40mg Dube MP. Lipid management. 2015. p. 241-255

Statin Selection +ART, continued NNRTI-, RAL-, or DTG-Containing Regimens High-Intensity Statins Moderate-Intensity Statins Low-Intensity Statins Atorvastatin 40-80mg Atorvastating 10-20mg Pravastatin 10-20mg Rosuvastatin 20mg Rosuvastatin 10mg Fluvastatin 20-40mg Pravastatin 40-80mg Pitavastatin 1mg Pitavastatin 2-4mg Lovastatin 20mg Lovastatin 40mg Simvastatin 10mg Simvastatin 20-40mg Dube MP. Lipid management. 2015. p. 241-255

ART to Avoid in High Cardiac Risk Patients Consider avoiding ABC- and LPV/r-based regimen Switch Boosted PI to DTG in suppressed patients with High CV Risk 2 Hyperlipidemia: Pl/r, AVC, EFB and EVG/c have been associated with increased serum lipids HTN medications: PI and COBI combos can interfere with the rhythm of the heart (PR or QTc intervals) Anticoagulants: Aspirin and Heparin no interactions; need to monitor all other medications for DDI 1. DHHS Guidelines: Antiretroviral Agents for Adults, https://aidsinfo.nih.gov/guidelines 2. Gatell JM, et al. IAS 2017. Abstract TUAB0102. Clinical Trials.gov. NCT02098837.

Hypertension and HIV Analysis of HTN in HIV infected patients from 1996-2013 1996: 1.68 cases/100 patients 2013: 5.35 cases/100 patients Key risk factors: Age Obesity Diabetes Renal insufficiency Nadir CD4+ cell count < 500 cells/mm 3 Okeke NL, et al. Clin Infect Dis. 2016; 63:242-248.

The Concept of Frailty Multisystem clinical syndrome that reflects biological rather then chronological age; regarded as the end-stage state 1 Associated with loss of functional homeostasis, inability to recover fully after stressors, and morbidity and excess mortality 1 Risk Factors: Mental Health, Obesity, Arthritis, Viral Hepatitis 2 1. Onen NF, et al. J Infect. 2009;59:346-352 2. Erlandson KM, et al. IAS 2011. Abstract TUPE124.

Frailty Phenotype Frailty Characteristic Shrinking Muscle weakness Poor endurance/exhaustion Slowness Low activity Clinical Criteria* Unintentional weight loss (>10 lbs) in prior year Poor grip strength Self-reported exhaustion Walking time per 15 ft Low kcal/week expenditure *frailty defined as presence of 3 criteria; prefrailty as presence of 1-2 criteria Additional Tools: FRAIL Scale, Clinical Frailty Scale Piggott DA, et al. J Gerontol A Biol Sci Med Sci. 2017;72:389-394

Frailty More Common in HIV Assessment of frailty in HIV-infected (n=521) and uninfected (n=513) patients in the AGEhIV cohort Kooij KW, et al. AIDS. 2016;30:241-250.

Frailty More Common in HIV, continued Assessment of frailty in HIV-infected (n=521) and uninfected (n=513) patients in the AGEhIV cohort Kooij KW, et al. AIDS. 2016;30:241-250.

Treatment for Frailty There is no treatment Preventative measures: Managing polypharmacy Exercise Nutrition Willig, AL, et al. The Silent Epidemic - Frailty and Aging with HIV. Total Patient Care HIV HCV. 2016;1(1):6-7.

Bone Health and HIV Frailty is more prevalent among HIV-infected vs HIV-uninfected individuals Fracture prevalence and low BMD is common among patients with HIV Some ART regimens have larger impact on BMD loss than others Backbone: consider FTC/TAF or ABC/3TC vs FTC/TDF Greater BMD loss observed with PI-based vs RAL-based regimens Avoid TDF DHHS Guidelines: Antiretroviral Agents for Adults, https://aidsinfo.nih.gov/guidelines

Recommendations for Evaluation of Bone Disease in HIV HIV-Infected Population Assessment Monitoring Men 40-49 yrs of age Premenopausal women 40 years of age Men 50 yrs of age Postmenopausal women Patients with fragility fracture history, receiving chronic glucocorticoids, or high risk of falls Assess risk of fragility fracture using the FRAX Assess BMD using DXA Brown TT, et al. Clinic Infect Dis. 2015;60:1242-1251. For patients with FRAX score 10%, monitor FRAX in 2-3 yrs For patients with FRAX score > 10% perform DXA For patients with advanced osteopenia monitor DXA in 1-2 urs For patients with mild or moderate osteopenia, monitor DXA in 5 yrs For patients started on bisphosphonates, repeat DXA in 2 yrs

Mental Health and HIV What is the cause? HIV or present prior to infection? Which condition takes treatment priority? Mental health medications have many DDI interactions with ART Mental health must be under control to achieve ART adherence ART regimen determines what mental health medications can be prescribed

Syphilis and HIV Syphilis incidence continues to increase within the HIV population HIV-infected patients with syphilis should have a detailed neurologic examination. Abnormal symptoms should undergo cerebrospinal fluid (CSF) analysis. Test for Neurosyphilis: neurological dysfunction (eyes or ears), Penicillin (IM, IV) is the treatment of choice for syphilis Workowski, KA, et al. Centers for Disease Control and Prevention. Sexually transmitted disease treatment guidelines, 2015. MMWR 2015;64:1-138.

HIV + HCV + Opioids Commonality between HIV, HCV and opioid epidemic Resources: AIDSVu: https://aidsvu.org HEPVu: https://hepvu.org amfar: http://opioid.amfar.org Indiana HIV outbreak in 2015 linked to IDU Over 140 cases reported that year

Substance Abuse and HIV COMPLEX!!!!! Substance abuse causative or a cofactor!?!?!? Substance abuse includes, but not limited to: Alcohol, opioids, cocaine/crack, methamphetamine, MDMA (ecstasy or molly), benzodiazepines, marijuana, ketamine, GHB, anabolic steroids, nitrate inhalants, barbiturates, nicotine, synthetic compounds

Substance Abuse and HIV, continued Team efforts for patient care Case management Primary care provider Substance abuse prescriber Mental health Pharmacists Must become substance free

HIV Diagnosis in the Aging HIV diagnosis at age 50 or greater Elderly population on the rise for STDs, HIV is no exception Prioritizing disease state management Initiating ART is different based on the aging of the body Polypharmacy is real!

DHHS: Initial Selection ART Based on Age-Related Co-morbidity Scenario Consider Avoiding Recommendation with Considerations CKD (efgr <60 ml/min) TDF, especially in RTV-containing regimens TAF (if egfr > 30 ml/min) ABC/3TC (HLA-B 5701 negative; 3TC need dose adjustment for CrCL < 50 ml/min) DRV/RTV + RAL (VL < 100,000 copies/ml and CD4+ > 200 cells/mm 3 ) LPV/RTV + 3TC (3TC need dose adjustment for CrCL < 50 ml/min) Osteoporosis TDF TAF ABC/3TC (HLA-B 5701 negative) CVD risk ABC Hyperlipidemia PI/RTV or PI/COBI EVG/COBI DTG RAL TDF

Pharmacists Managing HIV: Unlimited Potential Role Patient/caregiver educators Medication manager/polypharmacy Provision of adherence reminder device Synchronization of medications Coordination of refills Care plans/action plans/progress notes Pharmacy detective Collaborative practice protocols Point of care testing + link to care Outcomes Improved adherence to Medication Improved CD4+ and VL Patients more engaged Cost savings Decreased # visits to PCP/hospital

Stigma and HIV Very present and interferes with care/adherence Still believed it is a MSM disease Empower through HIV education Know how to prevent and know your status!

PrEP Game changer with stigma, depression and life style for HIV population Who should be on it? Men vs Women on PrEP Should children or young adults take PrEP What about our seniors?

Is There a Chance for HIV Cure?

Keeping Healthy HIV Patients Healthy Adhere to HIV mediations Quit smoking Refine diet and maintain normal weight Exercise Reduce alcohol intake; avoid recreational drugs 1. Hermsdorff HH, et all. Endocrine. 2009;36:445-451. 2. Bonato M, et al. BMC Infect Dis. 2017;17:61.

ART Tips for Older Pts ART is recommended for EVERYONE regardless of CD4 count Organ functions must be closely monitored Polypharmacy more likely to occur Collaboration between healthcare providers is important Focus: education, prevention and care DHHS Guidelines: Antiretroviral Agents for Adults, https://aidsinfo.nih.gov/guidelines

Questions? Thank you for your time!