Medication Adherence:What Can We Do to Help Patients Stick to Therapy

Lois Eldred, DrPH, MPH

Special Projects of National Significance

HIV/AIDS Bureau, HRSA

Viral Suppression in Clinical Practice

42 4437

0

20

40

60

80

100

Pro

port

ion

of P

atie

nts

wit

h V

L <

500

copi

es/m

l

1-90 days 3-7 months 7-14 months

Johns Hopkins' Moore Clinic Experience

Lucas, Annals Intern Med 1999

Adherence Critical to Care

Nonadherent patients with: Increased mortality from HIV

– OR 1.16 (1.06-1.26) / 10% adh 1

Lower CD4 count increase– + 6 versus +83 cell/ml increase 2

Increased hospital days– 12.9 versus 2.5 hosp. days / 1000 days F/U 2

1 Hogg, 7th CROI, 2000 2 Paterson, Ann Intern Med, 2000

How much adherence is enough?

1829 33

45

78

0102030405060708090

100

<70 70-79.9 80-89.9 90-94.9 >95

Adherence with Protease Inhibitor Therapy

Vir

al lo

ad <

400

(% p

atie

nts)

Paterson, Ann Intern Med, 2000

Viral Load by Adherence

10

33

61

80

0

10

20

30

40

50

60

70

80

90

100

<50 50-70 70-95 >95Adherence with Antiretrovirals

Pro

port

ion

of

Pati

ents

wit

h V

L <

400

c/m

l

Arnsten, 7th CROI, 2000

Viral load and adherence (MEMS)

74

88 87 85 8590

81

0

20

40

60

80

100

<70 >70 >75 >80 >85 >90 >95 Adherence level (%)

Pro

port

ion

of p

ts w

ith

VL

< 4

00

copi

es/m

l

Mostly women and minorities viral load <100,000 copies/ml, ARV naive

Thompson M, et al. XIII IAC, Durban 2000. Abstract 1129

Measuring Adherence

No gold standard Use what is practical

– Patient report will overestimate 30- 50%– Pharmacies can be your friend– Electronic monitoring in selected cases,

especially if it will help the patient– Drug levels not practical for adherence

monitoring

Factors in Adherence

Patient

Drug Regimen

Medical System

Predictors of Adherence: Patient

Understanding of the regimen Alcohol/drug use Depression Appointment keeping Health beliefs and attitudes Perception of control (self efficacy) Social support

Adherence and Illicit Drug Use

48

23

38

21

42

24

43

26

0

5

10

1520

25

30

35

40

4550

Mis

sed

>1 d

ose

in 3

day

s

Heroin Cocaine Binging Heavy Alcohol

UsingNot Using

Adapted Cheever, ICAAC, 1999

Drug Abuse Treatment Works

78

65

42

0 20 40 60 80 100

Proportion of Adherent Patients

Adherence with Antiretrovirals Among Drug Users

Active IDU

Ex- IDU (1)

BupenorphineMaintence (2)

1 OR 1.88 (0.69- 5.28)2 OR 4.91 (1.22-20.76)

Moatti, AIDS, 2000

Health Beliefs and Attitudes

Associated with antiretroviral (ARVs) use – ARVs will help me have fewer symptoms of

HIV – ARVs will help me live longer

Associated with adherence– Medications will often fit into daily routine– If don’t take right, resistance will develop

Paterson, Abs 92; Kaplan, Abs 96; Wenger, Abs 98; 6th CROI, 1999; Cheever, Abs 591, 39th ICAAC, 1999

Interventions to Improve Adherence

Barriers to adherence– Differ among patients – Vary over time

Principles of interventions– Multifaceted– Repetitive– Initiated prior to resistance developing

Self Efficacy Counseling to Improve Adherence

Randomized, controlled trial

Intervention:– Counseling to increase self efficacy– Strategies to increase adherence– Association of adherence and resistance– Telephone number for questions

Tuldra, JAIDS 2000

Self Efficacy Counseling to Improve Adherence

01020304050

60708090

100

Week 4 Week 24 Week 48

Pro

port

ion

of P

ts >

95%

Adh

.

Inter ATCntrl ATInter ITTCntrl ITT

Tuldra, JAIDS 2000

Factors in Adherence

Patient

Drug Regimen

Medical System

Adherence: Treatment Regimen

Number of doses, medications, pills

Length of time on therapy

Dietary restrictions

Side effects

Side Effects Impact Adherence

66

47

01020304050

60708090

100

<=2 Side Effects >2 Side Effects

Pro

port

ion

of A

dher

ent

Pat

ient

s (%

)

Arnsten, 7th CROI, 2000

Factors in Adherence

Patient

Drug Regimen

Medical System

Medical System Team support and interventions

Doctor- Patient relationship– Trust / satisfaction

Patient education– Appointment reminders– Multiple and varied reinforcers

Accessibility of appointments, medication– Child care / child friendly environment– Transportation

Engagement in Care Convenience Sample of 707 outpatients Engagement in care: Interaction with

health care provider (13 item scale)– Listens to me– Cares about me– Respects me– Spends enough time with me– Includes me in decision making

Bakken, AIDS Patient Care and STDs, 2000

Non-engaged Patients

More likely to be current/past injection drug users (p=0.002)

Nonadherent with – Medication taking– Medical appointments – Following medical advice

Not associated: type of provider, sex, race

Bakken, AIDS Patient Care and STDs, 2000

Satisfaction with Information

0102030

405060

708090

100

High Satisfaction Low Satisfaction

Proportion of Patientswith 95% Adherence

p=0.02

Tuldra, 7th Euro. Conf. Clin. Aspect. And Tx of HIV, 1999

Asking about Adherence:What works

Steele , J Fam Pract 1990

“You’re gaining weight. You must be taking your medicine okay.”

0%

“Any problems with your medicines?” 63%

“Almost everyone misses medicines some of the time. In the last (week/month) how many doses of medicine do you think you’ve missed?”

“Tell me exactly how you take your medicines.”

80%

Asking About Adherence

Permission for missed dose: Almost everyone misses medicines some of the time.

Specific questioning: In the last (week/month) how many doses of medicine do you think you’ve missed?

Verify understanding of regimen: Tell me exactly how you take your medicines.

Interventions to Improve Adherence: Background

Clinicians play a specific role and significant role in initiating and monitoring adherence

Adherence research and other diseases focuses primarily on physicians

Most HIV adherence interventions involve a team of providers

Improving Access to Care >1/3 of patients in U.S. sample (HCSUS)

went without medical care due to:1– Need for money for food/clothing/housing– Lack of transportation– Inability to get time off from job/work– Feeling too sick

Caring for others: Putting off care 2– Women OR 1.6 (1.2 - 2.2)– Having child in household OR 1.8 (1.4 - 2.3)

1Cunningham, Med Care 1999, 2 Stein Am J of Pub Health 2000

Support Services and Retention in Care

0

10

20

30

40

50

60

70

Support service

Pro

po

rtio

n o

f p

atie

nts

in

year

1 (

%)

With regular service

Without supportservices care

Sherer R, AIDS Care, 2002

n=2647

• 20% increase in regular visits (>2/year) in an urban clinic with support services, 1997-1998

Directly Observed Therapy

0102030405060708090

100

0 8 16 24 32 40 48

Time (weeks)

HIV

vir

al<5

0 c

opie

s/m

l (%

)

DOT

SAT

DOT = directly observed therapy (incarcerated cohort)SAT = self-administered therapy (free clinic cohort)

4

Fischl 7th CROI, SF, 2000. Abs 71

Interventions: Incentives Work

35

48

61

0102030405060708090

100

Pro

port

ion

Ret

urni

ng fo

r P

PD

Rea

ding

Standard Care Voucher Voucher +Education

Chaisson, JAIDS, 1996

Incentive to Improve Adherence

Randomized, controlled trial– MEMS device and AZT plasma levels

Intervention– Cue dose training– Feedback from MEMS device– Cash ($2/correct dose up to $10/day, $280 max.)

Rigsby, J Gen Intern Med 2000

Incentive to Improve Adherence

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20

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80

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Weeks

Ad

her

ence

(%

)

Cue dose + $Cue DoseControl

+ + + + +

Rigsby, J Gen Intern Med 2000

SPNS/HRSA Initiative: Adherence

14 Projects with varying adherence interventions (1999-2004)

Common core data evaluated among the projects

Evaluation Center: New York Academy of Medicine; Center for Adherence Support and Education (CASE)

CASE Findings “readiness” component helps client maintain

high levels of adherence Interventions based on Prochaska’s stages of

change helpful over 6 months No direct relationship between the intensity

of encounters and improvement in adherence Specific support and clinical services have

positive impact over time

Medication Support Versus Standard of Care: Johns Hopkins HIV Clinic

Nurse Education Case Management Peer Advocacy Group Education Results: High users of readiness program

more likely to achieve improved viral suppression (< 50)

Self Efficacy Counseling to Improve Adherence

Variable Odds Ratio CI p value

Self efficacy 13.76 1.2 – 188.1 0.04

Intervention group 6.58 1.1 – 39.5 0.03

Effort Index

5.38 1.1 – 25.4 0.03

Multivariate Analysis: Adh. >95% at 48 wks

Tuldra, JAIDS 2000

Adherence: Conclusions

Adherence is critical for long term success of HAART

Interventions must be maintained over time Barriers differ among patients and over time

interventions must be patient-tailored Adherence interventions are now a standard

part of quality HIV care

Adherence: Where do we go from here?

Needs assessment of readiness and active interventions to promote self-efficacy for taking medications

Collaborative approach in timing the initiation of medication

Group support and education is a powerful tool

Self-management Programs

Adherence: Where do we go from here?

Use experiences with other chronic disease self-management programs

Cost effectiveness must be demonstrated as adherence interventions are integrated into practice

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