Adherence Evidence-Based - C Behrens

8/13/2019 Adherence Evidence-Based - C Behrens

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Adherence to HIV Medications:An Evidence-Based Review

Christopher Behrens, MD

Northwest AIDS Education &Training Center

University of Washington


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Adherence

[physicians] should keep aware of the fact that

patients often lie when they state that they havetaken certain medicines."

- Hippocrates

Drugs dont work if people dont take them.- C. Everett Koop


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Adherence and Antiretroviral

Therapy

Measuring Adherence

Why Adherence Matters

antiretroviral efficacy

development of resistance

Factors associated with adherence

Interventions to improve adherence


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Current DHHS guidelines on

Initiation of Antiretroviral Therapy

The likelihood of patient adherence should be

discussed and determined by the individual patientand clinician before therapy is initiated.

Before the first prescription is written, patient

readiness to take medication should be clearlyestablished

August 2001 Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents


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Clinicians Estimates of Adherence

Not Much Better Than Random

Bangsberg 2001 JAIDS HAART

Paterson 2000 Annals Int Med HAART

Haubrich 1999 AIDS HAART

Steiner 1995 Arch Int Med AZT

Bosely 1995 Eur Resp J Inhaled terbutaline

Charney 1967 Pediatrics Penicillin

Caron 1978 Clin Pharmacol Anatacids

Gilbert 1980 Can Med Assoc J Digoxin

Blowey 1997 Ped Nephrology Cyclosporin

Mushlin 1977 Arch Int Med Hypertensive


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Provider Estimate vs.Three 3-Day Patient

Report Compared to Pill Count

Three 3-day Self Report and Pill Count Adherence

Pill Count

100806040200

Pa

tientReport

100

80

60

40

20

0

Provider Estimate and Pill Count Adherence

Pill Count

100806040200ProviderEstimate

100

80

60

40

20

0

Provider Estimate

R sq = 0.26Patient Report

R sq = 0.72Bangsberg et al JAIDS 2001:26:435

n=45


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Measuring Adherence:

Patient Self-Report

patients tend to report what they think the provider

wants to hear1

patients are unlikely to misrepresent high levels ofadherence3- hence, patient-reported poor

adherence is specific but not sensitive

patient-reported adherence tends to exceed

adherence by more objective measurements, suchas pill count or electronic monitoring2

1. DiMatteo MR, DiNicola DD, eds. Achieving Patient Compliance. New York: Pergamon Press; 1982:1-28.

2. Golin C et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago. Abstract 95.

3. Bond W, Hussar DA, Am J Public Health 1991;81:1978-1988.


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How Do Adherence Measurement

Techniques Compare to One Another?

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7080

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100

Self-Report Clinician

Estimate

Pill Count Electronic

bottle cap

ADEPT Study; N=81 patients

Adapted from Golin C et al. 1999; Miller L et al. 1999.

Adh

erence,

%


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Patient Self-Report

Nevertheless, studies have documented an

association between patient-reported adherenceand viral outcome1-3

patient-reported adherence may be a useful tool to

evaluate adherence at a group level but not somuch on an individual level

1. Bangsberg DR, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago. Abstract 93.

2. Duong M, et al. 39th ICAAC; 1999; San Francisco. Abstract 2069

3. Demasi R, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago. Abstract 94.


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Measuring Adherence: Diaries

In theory, better than relying on memory

in practice, not very useful

many patients do not fill them in1

those that do may do so immediately before

office visit

1. Golin C, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago. Abstract 95.


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Pill Counts

Advantages:

more objective than

patient report correlates better with

electronic bottle caps

than does self-reported

adherence1

1. Golin C, et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago. Abstract 95

Drawbacks:

many patients forget to

bring their bottlespatients can still

exaggerate adherence

time consuming

patients may find it toopaternalistic

does not reveal patterns

of missed doses


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Laboratory Markers

many antiretroviral agents associated with

changes in laboratory parameters

AZT, d4T produce macrocytosis

indinavir associated with hyperbilirubinemia

didanosine changes urinary uric acid levels

drug levels could also potentially be used to

monitor adherence


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Laboratory Markers to Assess

Adherence: Drawbacks

lab markers not highly sensitive nor specific

do not give any information regarding the pattern

of non-adherence

patients who take their medications immediately

before having blood levels drawn could

exaggerate their adherence

measurement of drug levels has not been

standardized

other factors besides adherence can affect drug

levels


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Electronic Bottle Caps

caps harbor chips that register each time a

bottle is opened or closed

MEMScaps, Aardex Corp.


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QuickRead software, for use with MEMScaps system

http://www.aardex.ch/QRCalendar.htm


17/65http://www.aardex.ch/QRChronology.htm

QuickRead software, for use with MEMScaps system


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Electronic Bottle Caps

Advantages

more difficult for

patients to exaggeratetheir adherence

reveals patterns of non-

adherence

studies using thesedevices have

documented

relationship between

adherence & dosing

Disadvantages

too expensive for

routine use outside ofresearch studies

cannot be used for

patients who use

pillboxes


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The Future of Adherence Assessment?

Computer-Assisted Self-Interviewing (CASI)

Advantagesof CASI

Privacy may improve disclosure

Visual ARV recognition

Standardizes adherence assessmentNot personnel intensive

Could be administered in waiting

room or at home

via the web

Bangsberg D et al. AIDS Care, 2002 (in press)

Purposes of CASI

Determine patients understanding of medication regimen

Determine patients adherence over 3-day period

http://www.edermpda.com/hivadhere/


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Printed with permission from

West Portal Software Corp.


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Pilot CASI Adherence Measurement

111 patients, 11 providers in study

over 50% of patients made at least one error in

describing their regimen

providers missed 76% of non-adherent patients

patients reports of adherence significantly

associated with viral load counts 65% of patients reported that CASI made them

think more about how they take their medications

Bangsberg, Bronstone & Hoffman AIDS Care 2002 (in press)


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Why is Adherence so Importantfor Antiretroviral Therapy?

I. Efficacy

II. Resistance

V l C l f ll h l h


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Virologic Control falls sharply with

diminished adherence

0

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5060

70

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90

95-100% 90-95% 80-90% 70-80% < 70%

Adherence, by prescription refill

%A

chie

ving95 90-95 8090 70-80


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10% Adherence difference = 21% reduction in risk of AIDS

Adherence and AIDS-Free Survival

Bangsberg D, et al. AIDS. 2001:15:1181

ProportionA

IDS-Free

Months from entry

P= .0012

0 5 10 15 20 25 30

0.00

0.25

0.50

0.75

1.00

Adherence

O 90100%

O 5089%

O 0

49%


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Adherence & Drug Resistance

HIV Reverse Transcriptase (RT) is error-

prone

on average, HIV RT generates one mutation

in each copy of HIV produced

billions of HIV virions produced daily in

untreated patients

some HIV mutations associated with drug

resistance


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Sub-Optimal Adherence Predisposes

to Resistance

Sub-optimal adherence ==> sub-therapeutic

drug levels ==> incomplete viral

suppression ==> generation of resistantHIV strains by selection for mutant viruses

association between poor adherence andantiretroviral resistance well-documented1,2

1. Vanhove G, et al. JAMA. 1996;276:1955-1956.2. Montaner JS, et al. JAMA. 1998;279:930-937.


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What Contributes toSub-Optimal Adherence?

f dh


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Reasons for Non-Adherence:

Clinician vs Patient Views

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value,%

No. of doses or

pills

Side Effects Meal Instructions Schedule

complexity

Other

Clinican

Patient

Chesney M. Adherence to antiretroviral therapy. 12th World AIDS Conference, 1998; Geneva. Lecture 281


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Predictors of Poor Adherence

active alcohol1or substance2abuse

work outside the home for pay1

depressed mood1

lack of perceived efficacy of HAART3

lack of advanced disease4

concern over side effects4

1. Chesney MA. 37th ICAAC, 1997; Toronto. Abstract 281.

2. Cheever LW, Curr Infect Dis Rep 1999 Oct;1(4):401-407.

3. Horne R, et al. 39th ICAAC, 1999; San Francisco. Abstract 588.4. Wenger N, et al. 6th Conference on Retroviruses and Opportunistic Infections, 1999; Chicago. Abstract 98.

P d f P Adh


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Predictors of Poor Adherence,

continued

non-caucasian race documented in some

studies1-3but not others5

association of race with adherence not found in

other disease states

lower literacy rate a confounder?4

1. Paterson, et al.6th Conference on Retroviruses and Opportunistic Infections, 1999; Chicago, IL. Abstract 92.

2. Wenger N, et al. 6th Conference on Retroviruses and Opportunistic Infections, 1999; Chicago, IL. Abstract 98.

3. Mar-Tang M, et al. J Gen Intern Med. 1999;14(suppl 2):53.

4. Kalichman SC, et al. J Gen Intern Med. 1999;14:267-273.5. Stone VE, et al. JAIDS 2001; 28:124-131

P di f P Adh


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Predictors of Poor Adherence,

continued

inability to fit medications into daily

schedule

tid dosing, food requirements1

1. Stone VE, et al. JAIDS 2001; 28:124-131


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Other Considerations

a large proportion of patients incorrectly

recall their medication schedules1,2

Virologic control does not necessarily imply

high levels of adherence3

patients with virologic control despite poor

adherence may not maintain durable viralsuppression without improved adherence

1. Chesney MA, International AIDS Society USA Meeting, 1998; Los Angeles.

2. Kravitz RL, et al. Arch Intern Med. 1993;153:1869-1878.

3. Kaplan A, et al. 6th Conference on Retro-viruses and Opportunistic Infections; 1999; Chicago. Abstract 96.

F A i d i h Hi h


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Factors Associated with Higher

Levels of Adherence

twice-daily or once-daily regimens1,4

belief in own ability to adhere to regimen1

not living alone2

dependent on a significant other for support2

history of Opportunistic Infection or AdvancedHIV disease3

1. Eldred L, et al, J Acquir Immune Defic Syndr Hum Retrovirol 1998;18:117-125.

2. Morse EV et al, Soc Sci Med 1991;32:1161-1167.3. Singh N, et al, AIDS Care 1996;8:261-269.

F A i d i h Hi h


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Factors Associated with Higher

Levels of Adherence

Belief in efficacy of antiretroviral therapy

Belief that non-adherence will lead to viral

resistance

Wenger N, et al. 6th Conference on Retroviruses and Opportunistic Infections, 1999; Chicago. Abstract 98.

I i Sh I


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Interventions Shown to Improve

Adherence to Antiretrovirals

medication alarms1

education & counseling sessions2,3

Directly Observed Therapy (DOT)4,5

1. Samet JH, et al. Am J Med. 1992;92:495-502.

2. Malow RW, et al. Alcohol Drug Abuse 1998;49:1021-4.

3. Tuldra A, et al. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999; Abstract 595.

4. Sorensen JL, et al. AIDS Care. 1998;10:297-312.

5. Wall TL, et al. Drug Alcohol Depend. 1995;37:261-269.


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Self-Adminstered vs Directly Observed

Therapy During Incarceration

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Adherence Evidence-Based - C Behrens

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