Optimizing Health Care in the Context of Multimorbidity,

Polypharmacy, and Decreasing Physiologic Reserve

Amy C. Justice, MD, PhDSection Chief, General Internal Medicine

VA Connecticut Healthcare SystemProfessor of Medicine and Public Health

Yale University

Multimorbidity

HIV Has Never Occurred in a Vacuum

• Irrespective of aging, HIV care complicated by:

– Multi drug regimens susceptible to non adherence, resistance, and toxicity

– Co infections (HCV, TB, MDR-TB)– Socio economic issues: stigma, substance addiction,

incarceration, homelessness, under nutrition

• Aging adds multiple chronic diseases (multimorbidity) to mix

Multimorbidity and Age in HIV+ South Africans

WHO Survey “Study of global AGEing and adult health (SAGE), South African subjects” Data are restricted to those with HIV infection. Negin J. et al. AIDS 2012 26(S1):S55-63

% P

revalence

Incident Chronic Disease: Swiss Cohort 2008-10

Of 1,189 events in 8,444 patients, only 16% were HIV events, 84% were Non HIV:

Hasse B. et al. Morbidity and Aging in HIV-Infected Persons: The Swiss HIV Cohort Study CID 2011 53:1130-1139

Limit of Silos: Coordination

and Communication

Accelerated or Accentuated?

A. Accelerated and Accentuated: cancer occurs earlier among those with HIV than uninfected comparators and there are more cancer events.

B. Accentuated risk: cancer occurs at the same ages but more often than among comparators.

Shiels MS. Ann Intern Med 2010:153:452-460.

Age at Onset of Cancer AIDS Patients and Age Matched Uninfected Individuals

Cancer AIDS HIV- Age AdjustedHIV-

ApparentDifference

Real Difference

Rectal 46 69 51 -23 yrs -5 yrs

Anal 50 62 54 -12 yrs -4 yrs

Larynx 48 65 52 -17 yrs -4 yrs

Lung 50 70 54 -20 yrs -4 yrs

Ovarian 42 63 46 -21 yrs -4 yrs

Testicular 35 34 38 +1 yr -3 yrs

Hodgkinlymphoma

42 37 40 +5yrs +2 yrs

Myeloma 47 70 52 -23 yrs -5 yrs

Shiels MS. Ann Intern Med 2010:153:452-460.

Looked at 26 different diagnoses, no difference (p>0.05) for 18 cancer. Differences for remaining cancers were <5 years.

Age at Diagnosis in VACS Comorbid

DiseaseSource HIV+

(yrs)HIV-(yrs)

Difference

LungCancer

Medapalli RK. AIDS 2012;26(8):1017-25

57 59 -2

Myocardial Infarction

Kaku A. CROI 2012 oral # 120 56 56 0

Renal Failure (eGFR<45)

J Acquir Immune Decif Syndr 2012; 60(4):393-9

59 63 -4

FragilityFracture

Womack J. PloS ONE 2011;6(2):e17217

IAC 2012: MOPE087, Womack J.

54 53 +1

Symptomatic Liver Cirrhosis

IAC 2012: WEABO 102, Lore V. 57 58 -1

See also: IAC 2012 TUPE160 Shiels M. Age at Cancer Diagnosis in HIV+ in North America Compared to General US Population

Polypharmacy

Polypharmacy• Typically defined as >5 drugs

• Associated with diminished marginal benefit from additional medication due to:– Nonadherence– Adverse drug events (confusion, falls, renal failure, etc.)

• Risk of adverse events increases approximately 10% with each additional medication

Salazar JA. Expert Opin Drug Saf (2007) 6(6):695-704 Gandhi TK. N Engl J Med 2003;348:1556-64

Decreasing Physiologic Reserve

Disability, Frailty, and Functional Status• 3 geriatric concepts increasingly applicable to

those aging with HIV

• Each is a consequence of total physiologic injury rather than of any particular diagnosis

• Of note, these concepts also relate to cognitive dysfunction, especially delirium and dementia

Index ScoreRestricted VACS

Age (years) <50 0 050 to 64 23 12> 65 44 27

CD4 > 500 0 0cells/mm3 350 to 499 10 6

200 to 349 10 6100 to 199 19 1050 to 99 40 28< 50 46 29

HIV-1 RNA < 500 0 0copies/ml 500 to 1x105 11 7

> 1x105 25 14

Hemoglobin > 14 0g/dL 12 to 13.9 10

10 to 11.9 22< 10 38

FIB-4 < 1.45 01.45 to 3.25 6> 3.25 25

eGFR mL/min > 60 045 to 59.9 630 to 44.9 8< 30 26

Hepatitis C Infection 5

Age

HIV SpecificBiomarkers

Biomarkers of General Organ System Injury

VACS Index Thresholds and Weights

VACS.MED.YALE.EDU

VACS Index• Predicts mortality:

– All Cause, HIV, and non HIV (European Data)– Risk of mortality over 5 years (North American Data)

• Predicts morbidity: hospitalization, MICU admission, and fragility fractures

• Correlated with functional performance and symptom burden

• Responsive to changes in risk after ART initiation, intensification, and interruption

For more information and full documentation go to: www.vacohort.org To use/comment on the VACS Index Calculator go to: HTTP://vacs.med.yale.edu

We Need a “Map” to Optimize Care• A comprehensive outcome to compare

effectiveness of interventions and identify those with the best benefit/harm ratio

• A means of combining interventions into a strategy for medical patients with multimorbidity

• A means of motivating and guiding patients and providers to pay attention to that which matters most for patient outcomes

Health Risk Assessment: A Means of Navigating Complexity

• Identify and prioritize modifiable risks among a lengthening list of possibilities

• Motivate and map progress• Quantify harm and benefit from interventions

– Level of susceptibility to adverse drug events– Short term risk of hospitalization– Risk of disability, assisted living requirements

• Identify end of life to signal change in priorities

We Have a Sense for 50-64 yrs,But 65+ Remains Uncharacterized

Relative Risk of Incident Disease at 50-64 and 65+ Compared with <50 Yrs

Rel

ativ

e R

isk

(HR

)

Hasse B. et al. Morbidity and Aging in HIV-Infected Persons: The Swiss HIV Cohort Study CID 2011 53:1130-9

End of Life• With aging inevitably comes end of life

• Aging patients want to know when they are within 5 years of death to:1

– Prepare– Make the most of remaining life– Make medical/health-related decisions

1. Ahatt C. et al. “Knowing is Better”: Preferences of Diverse Older Adults for Discussing Prognosis. J Gen Intern Med 2011, 27(5):568-75

Conclusions• Multimorbidity is common for those aging with HIV and

requires a new approach to care and research– Individual diagnoses less important than cumulative injury– We need tools to assess injury and its impact

• In the context of polypharmacy and physiologic injury, additional medication may cause more harm than good– Need to consider what medications are most essential

• Ongoing risk assessment, evidence based prioritization, and coordination of care must become the new bywords

Research Priorities• Study mechanisms in multimorbidity:

– “Multi-hit” (cancer) and “cumulative frailty” (geriatrics)– Develop a standard approach to measuring physiologic injury– Compare HIV+/- to determine whether HIV has distinct

mechanisms of injury

• Compare harms and benefits of additional treatment and of decreased treatment

• Consider alternative ways of organizing and delivering care in the context of multimorbidity

• Test whether care prioritized based upon risk, benefit, and preferences is more effective than UC

Two Studies in General Population Illustrate the Tension in Studying

Aging and HIVSTOPP

Polycap

RESULTS• Unnecessary drugs decreased 36%• Underutilization of indicated drugs

decreased by 21%• Improvements sustained for 6 mos.• No significant differences in deaths,

falls, readmission, LOS, or f/u outpt visits—all but readmissions less in intervention arm (but not significant)

METHODSRandomized 400 hospitalized patients aged 65+ yrs. to receive either usual care or screening with STOPP/START criteria with follow up recommendations to providers.

• 2007-2008• 2,053 subjects; 50

centers in India• 45-80 yrs; 1 risk factor• Not on medication• Aspirin, thiazide,

ramipril, atenolol, and simvastatin

• Outcome: BP, LDL, heart rate, urine biomarker for plt. act.

• ADE: discontinuation

Yusuf S. Lancet 2009; 373:1341-51.

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