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
0
20
40
60
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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