12/2/2016 Medication Challenges in the Disclosures Aging HIV - - PDF document

12/2/2016 1 Disclosures

• Unrestricted educational grants:

– Abbvie, Bristol Myers Squibb, Gilead, Merck, ViiV

• Speaker honoraria/consulting:

– Abbvie, Gilead, Merck

• Advisory board:

– ViiV

Medication Challenges in the Aging HIV Population

• Comorbidities/polypharmacy
• Drug interactions
• Adherence
• Retrospective, observational

study

– People with HIV, ≥18 yrs age (04/92‐03/09) versus non‐ infected adults in Ontario – Comorbidities: mental health condition, diabetes, CHF, acute MI, stroke, HTN, asthma, COPD, PVD, ESRD

• Results:

– HIV cohort (N=14,005): mean age 45.36 yrs, 80.5% male, urban setting (89.7%), lower income, 62.8% ODB – People with HIV had significantly higher prevalence of all chronic conditions except MI & HTN compared to the general population

HIV cohort (n=14,005) ON cohort (n=71,410) HIV:ON Prevalence (%) Prevalence (%) Prev. ratio 95% CI Mental Health cond. 40.55 21.99 1.84 1.75, 1.94 Hypertension 19.33 20.29 0.95 0.88, 1.04 Asthma 15.90 12.13 1.31 1.20, 1.43 Diabetes 9.65 8.13 1.19 1.06, 1.33 COPD 8.33 5.33 1.56 1.39, 1.76 CHF 3.35 1.49 2.26 1.74, 2.92 ESRD 1.96 1.76 2.57 1.92, 3.44 Stroke 1.55 1.01 1.53 1.15. 2.03 Acute MI 1.19 1.06 1.12 0.78, 1.60 PVD 0.63 0.29 2.15 1.35, 3.40 ≥1 physical condition 38.72 34.23 1.13 1.07, 1.20 Physical + mental 16.98 9.49 1.79 1.65, 1.94 Multimorbidity (≥2) 14.49 11.13 1.30 1.18, 1.44

High Burden of Metabolic Comorbidities in a Citywide Cohort of HIV Outpatients

• Adults with HIV in DC cohort (N=7018), median 50

yrs age, 18%>60 yrs, 73% male, 77% black, 97% ART‐ exposed, median 12.3 yrs since HIV diagnosis

Levy et al. 7th HIV Aging Wksp, 2016, O_9.

• n=10,265 HIV‐infected and 2,219,232 HIV‐negative

adults from the National Cancer Data Base, 2003‐ 2011

• HIV‐infected patients with cancer were more likely

to lack cancer treatment compared to HIV‐negative adults

– Head & neck, upper GI, colorectum, lung, breast, cervix, prostate, Hodgkin’s lymphoma and DLBCL (multivariate analysis, all p statistically significant) – Differences remained significant even when controlling for insurance

Suneja et al. Cancer 2016;122:2399-407.

• Older patients (50+ yo) more likely to:

– Be on more drugs than younger patients (9 vs 7, p<0.0001) – have clinically significant drug interactions than younger patients (71% vs 55%, p<0.0001) – A 10‐year increase in age associated with increased likelihood of ≥1 PDDI (OR 1.72, p<0.0001)

12/2/2016 2

Older HIV+ Patients More Likely to be On Treatment for Comorbid Conditions

<50 years (n=498) ≥50 years (n=416) P value Anti-infective 36% 45% <0.0001 CAM 5% 9% 0.01 GI medications 49% 66% <0.01 CV medications 26% 65% <0.0001 Anticoagulation/anti-platelet 3% 6% <0.01 Systemic hormonal agents 10% 16% <0.01 MSK agents (incl. osteoporosis) 10% 20% <0.0001 Narcotics/analgesics 23% 39% <0.0001 Antidepressants 19% 25% 0.04 Psychotropics 21% 29% <0.01

[Tseng A et al. Ann Pharmacother 2013;47:1429‐39.]

Medication‐Related Problems in HIV‐ Infected Adults Over the Age of 60

• N=89 (91% Caucasian, 94% male, median age 64, median 13

medications (2‐38), 4 ARVs

• Age/sex‐matched controls (n=28): median 6 medications

(p=0.03)

Greene et al. J Am Geriatric Soc 2014;62:447‐53. 52% 70% 17% 96% 74% 29% 4% 29%

P<0.01 P=0.03 P=0.07

Potential Consequences of Polypharmacy and Drug Interactions

• 1329 HIV+ patients receiving care between 2000‐2013

– Average 47 years old, 5 (3‐7) comorbidities, 3 (1‐5) non‐HIV meds – 34% PI, 46% NNRTI, 29% InSTI regimens

• 128 (9.6%) had a contraindicated drug‐drug interaction (XDDI)
• 214 (16.1%) patients hospitalized in first year of starting cART
• Patients with XDDIs had a significantly higher probability of

being hospitalized than patients without an XDDI

[Jakeman et al. ICAAC 2015, H‐780] Slide 15 209 admissions in which an ARV was prescribed for HIV+ patient Review of Records: 89 potential errors in 77 admissions (25.8%)

17 patients (19%) given HAART > 24h after admission

44 patients (49%) given incorrect dose or frequency

15 patients (17%) received < 3 antiretrovirals

13 patients (15%) received contraindicated combination of drugs 12 patients received contraindicated drug for > 24h*

1 error corrected within 24h

* 6 – Simvastatin + boosted PI 6 – PPI + Atazanavir OR (CI) 3.6 (1.8-7.3) 4.5 (2.6-8.1) 3.9 (1.9-8.1) 4.6 (2.6-8.1) 2.8 (1.4-5.3) 5.5 (3.1-9.8)

12/2/2016 3

• n=967,

mean age 51 (46‐56), 19% female, 48% white, 92% VL<50

• 18% had ≥1

fall in past 18 months

• 7% had

recurrent falls

• 5.2%

experienced fracture as a result of fall

ACTG A5322:

Tassiopoulos, HIV & Aging Wksp 2016, O_8

Co‐medication Use Has a Negative Impact on ART Continuity & Adherence

• Patients with non‐ART polypharmacy are

more likely to stop or change ART than patients not experiencing polypharmacy (36.8% vs 30%, p<0.01)

• Polypharmacy is a predictor of ART non‐

adherence (multivariate analysis)

Krentz et al. AIDS Pt Care STDs 2016;30:1‐7. Cantudo‐ Cuenca et al. J Manag Care Pharm 2014;20:844‐50.

Incomplete adherence to modern HAART over time is strongly associated with increased mortality

• Hazard ratio for mortality of 903 patients with HIV,

stratified by adherence initial regimen.

 Vertical bars=95% CI

Lima et al. J Acquir Immune Defic Syndr 2009;50:529–536.

• Mr. LF
• Saquinavir/ritonavir BID, tenofovir/emtricitabine
• Atorvastatin
• Inhalers: tiotropium (Spiriva), indacaterol (Onbrez)
• New Rx:

– tamsulosin (Flomax) – carbidopa‐levodopa (Sinemet) – citalopram (Celexa)

• Mr. LF: Drug Interaction Considerations
• Ritonavir inhibits CYP3A4, P‐gp, induces

CYP1A2, 2B6, 2C9/19, UGT

Metabolism Potential Interaction Management Tamsulosin CYP3A4  tamsulosin Strong CYP3A4 inhibitors contraindicated. *based on PK studies, could consider 0.4 mg dose with monitoring Carbidopa‐ Levodopa Decarboxylation, O‐methylation> transamination,

• xidation

Possible  carbidopa‐ levodopa Case report of levodopa toxicity (incl. severe dyskinesias) with indinavir use & rechallenge. Use with caution. Citalopram CYP2C19, 3A4 Possible  citalopram Use with caution; citalopram dose reduction may be necessary

• Mr. LF: DDI Considerations
• Pharmacodynamic:
• Drug‐Disease:

– Boosted PI + dyslipidemia; tenofovir DF + renal, bone?

12/2/2016 4 Impact of Aging on Drug Disposition and Tolerance

Pharmacokinetics:

• Renal insufficiency:

– Cockcroft‐Gault for dosing

• Hepatic dysfunction

– use Child‐Pugh for dose adjustment – e.g., abacavir, NNRTIs, PIs

Pharmacodynamics:

• More predisposed to ADRs

–  sensitivity to central & peripheral anticholinergic s/e –  benzodiazepine clearance –  baroreceptor responsiveness (, ‐blockers, ‐agonists) –  CNS sensitivity to opioids and sedatives

• Avoid or use certain drug

classes with caution

[Abrass et al. HIV & Aging Consensus Project, 2011.]

Impact of Aging on Medication Taking

• Older patients often have better adherence

rates compared to younger patients

• However, other possible challenges:

– Managing side effects – Scheduling HIV medications with other drugs – Changes in vision/hearing (labels, counselling) – Dexterity: opening pill vials, containers – Mobility: picking up refills – Memory: remembering to take medications – Financial: Rx deductibles, dispensing fees

Polypharmacy in the Older HIV Population: A Double‐Edged Sword?

More common compared to younger patients:

• Often more HIV‐treatment

experienced

– may require more complex regimens due to resistance – may not be candidates for STRs

• Higher rate of age‐related

comorbidities versus age‐ matched controls

But still not enough?

• Potential under‐

treatment of non‐HIV related comorbidities

• Lack of care

coordination

• treatment bias?

Optimizing Medication Use in the Aging Population

• 1. Simplify/Update ART
• E.g FDCs, STRs, once daily dosing, etc.

– Fewer pills, adherence, fewer dispensing fees

• Select drugs with good tolerability and

low interaction potential

• May be limited by ARV resistance
• May need to consider non‐traditional

ART combinations

• 2. Co-morbidity Prevention &

Treatment

• Ensure access to gold standard of care.

– HIV is not an exclusion to treatment or a reason for suboptimal treatment!

• Managing ART + co‐medications:

– Dose‐adjust/monitor for efficacy & toxicity – Consider alternative therapeutic options

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• 3. Home Organization
• Medicine cabinet clean‐up
• Annual brown‐bag visit
• OT consult? Social/family supports
• 4. Consolidate Care/

Manage Transitions in Care

• Encourage use of single pharmacy
• Communicate/plan with other care

providers

• Medication reconciliation (annual
• utpatient, hospital

admissions/discharge)

• Communication between providers is

essential!