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Adherence to HAARTAdherence to HAART
Adherence SummaryAdherence Summary
• Adherence is the Achilles Heel of HAART
• Adherence requires education, a shared negotiation, & the optimal regimen for the individual patient
• Simplify the regimen, BID or better, and anticipate, inform, and treat common side effects as part of adherence readiness
• Access to trusted, knowledgeable MD & health care team is essential
G Friedland and the CORE AETC NRC Training SlideAETC NRC Training Slide
For the Primary HIV Clinician: Too Much to Do, Too Many Questions
For the Primary HIV Clinician: Too Much to Do, Too Many Questions
• 20 HIV prevention
• Housing, nutrition
• Family & reproductive
counseling
• Chemical dependency
• Co-morbidities: Hepatitis C
• O.I. prophylaxis
• Goals of ARV therapy
– HHS Guidelines 1/00
• Adherence
• When to start, with what?
• When to change?
• Drug toxicities
• Rx of experienced pts
• Resistance testing
• Immune reconstitution
AETC NRC Training SlideAETC NRC Training SlideR. Sherer
The Extent of Non-AdherenceThe Extent of Non-Adherence
• Diabetes - 40-50%.
• Epilepsy - 30-40%.
• Hypertension - 40%.
• Asthma - 20%.
• Transplant - 18%.
• Oral contraception - 8%.
Non-Adherence Rates by Medication TypeNon-Adherence Rates by Medication Type
• Antiarrythmics - 76%
• Chemotherapy - 73%
• Antibiotics - 67%
• Antiasthmatics - 54%
• Antihypertensives - 47%
• Lipid lowering agent - 43%
• Anticonvulsants - 24%
• Immunosuppresants - 18%
PrescriptionsPrescriptions
• 1.8 Billion prescriptions annually.
• Over half of all prescriptions are taken incorrectly.
• 21% never get their prescriptions refilled.
• 11% of all hospital admissions are due to patients improperly taking their drugs
Factors that Influence AdherenceFactors that Influence Adherence
• Consistently predictive of non adherence – Symptoms and side effects– Negative life events/stress– Complexity of regimen
• Consistently predictive of adherence– Family or social support– Self-efficacy
Ammassari,JAIDS 2002
Factors that Influence AdherenceFactors that Influence Adherence
• Inconsistently predictive of adherence or non adherence
– Age, race, Income– Unstable housing– Active injection drug use– Alcohol consumption– Depression– Psychiatric co-morbidity– Health related quality of life– CD4 cell count– Dosing frequency– Knowledge and beliefs about treatment– Patient satisfaction with healthcare/patient-provider
relationshipAmmassari, JAIDS 2002
Factors that Influence AdherenceFactors that Influence Adherence
• Factors not predictive of adherence or non adherence– Gender– Education– Living with others/children– Unemployment– Medical insurance– Risk factor for HIV– History of injection drug use– Length of HIV infection– CDC disease stage– Naïve to ART– Number of antiretrovirals– Type of ARV drugs– Number of pills
Ammassari, JAIDS 2002
Adherence in IVDUsBouhnik, JAIDS, 2002
Adherence in IVDUsBouhnik, JAIDS, 2002
• Ex IVDU not in drug treatmentN=114
– 25% non adherence
– 14.9% high social instability– 37.7% medium social
instability– 47.4% low social
instability
• Current IVDU /in drug treatmentN=96
– 36% non adherence
– 31.3% high social instability
– 55.2% medium social instability
– 13.5 low social instability
Behavioral Correlates of AdherenceICoNA, JAIDS 2002
Behavioral Correlates of AdherenceICoNA, JAIDS 2002
Demographic Adherent n=298 Non adherent n=67
p value
Age 37.4 34.4 .001
Education < 8 years
55.2% 70.1% .025
Undetectable Viral Load
68.0% 40.4% .001
Side effects 38.9% 50.0% .001
Non injection drug use
5.4% 26.5% .001
Current IV drug use
4.7% 22.1% .001
Physician Estimate vs Measured AdherencePhysician Estimate vs Measured Adherence
Study PatersonAnn Int med 2002
HaubrichAIDS 1999
MillerRetrovirus, 1999
BangsbergJAIDS 2001
AdiCONAAthens, 2001
WagnerJ Clin Epi 2001
Enrollment N=81 N=173 N=73 N=45 N=320 N=793
Measure ofadherence
MEMS Patient report
MEMS Un -announced pill count
Patient report
Patient report
Dis-cordance of estimates
41% 45% 41% 40% 34% 39%
Adherence and HAARTAdherence and HAART
• NNRTI vs PI based regimens– 51% non adherence - PI– 38% non adherence –NNRTI– 41% lower risk of non adherence with NNRTI
• Compared with PI regimen– OR 0.53 Efavirenz non adherence– OR 0.63 Nevirapine non adherence
AdICoNA and AdeSpall studies, JAIDS 2002
Weeks 40–52 HIV RNA* vs baseline HIV RNA
*Lower limit = 20 copies/mL.*Lower limit = 20 copies/mL.Source: Montaner, Source: Montaner, et al. JAMAet al. JAMA 1998;279:930. 1998;279:930.
Baseline HIV RNABaseline HIV RNA(log(log1010 copies/mL) copies/mL)
NVP + ddI + AZT
AdherentNonadherent
-5.0
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2 3 4 5 6
HIV
RN
AH
IV R
NA
chan
ge f
rom
bas
elin
ech
ange
fro
m b
asel
ine
(log
(log
1010 c
opie
s/m
L)
cop
ies/
mL
)
What Degree of Adherence Is Needed?What Degree of Adherence Is Needed?
AETC NRC Training SlideAETC NRC Training Slide
Adherence to a PI-containing regimen correlates with HIV RNA response at 3 months
0
20
40
60
80
100
<70 70–80 80–90 90–95 >95
Pat
ient
s w
ith
HIV
RN
A<
400
cop
ies/
mL
, %
PI adherence, % (MEMScaps)
Source: Peterson, Source: Peterson, et al.et al. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago, IL. Abstract 92. 6th Conference on Retroviruses and Opportunistic Infections; 1999; Chicago, IL. Abstract 92.
What Degree of Adherence Is Needed?What Degree of Adherence Is Needed?
AETC NRC Training SlideAETC NRC Training Slide
Several trials indicate the need to achieve better viral suppression, i.e. < 50 cps/ml
Several trials indicate the need to achieve better viral suppression, i.e. < 50 cps/ml
AVANTI-2 (AZT/3TC/IDV)INCAS (AZT/ddI/NVP)
484032261680
100
0
20
40
60
80
0 8 16 24 32 40 48
0 8 16 24 32 40 48
All trials combined
Weeks
00 8 16 24 32 40 48
20
40
60
80
100AVANTI-3 (AZT/3TC/NFV)
Weeks
Pro
port
ion
of
su
bje
cts
wit
h
su
sta
ined
vir
olo
gic
su
ccess*
(%) Viral load Nadir
20 copies/ml21–400 copies/ml>400 copies/ml
*HIV-1 RNA <1000 copies/mlMontaner J. 12th World AIDS Conference Geneva 1998
AETC NRC Training SlideAETC NRC Training Slide
Cochrane Review of Adherence InterventionsCochrane Review of Adherence Interventions
• Adherence interventions for all types of diseases• Limited to Randomized Controlled Trials without confounding• Two HAART trials fit the criteria for inclusion• Many HAART trials excluded due to:
– Limited follow-up time– Confounding– Missing data– Significant lost to follow up– Adherence intervention unclear– Lack of a control group
Cochrane Reviewed HAART Adherence Interventions
Cochrane Reviewed HAART Adherence Interventions
• Knobel, Enferm Infecc Microbiol Clin 1999• Study design
– ZDV+ Lamivudine + Indinavir + conventional care– ZDV + Lamivudine+ Indinavir + counselling and adaptation of treatment to
patient lifestyle, telephone support, detailed medication information– Adherence measured by pill count, structured interview– Compliance =
• 90% drugs taken• > 90% meds taken according to schedule• < 2 mistakes in pill intake /day
• Study impact– Positive effect on adherence– Reduced viral load
Cochrane Review of Adherence InterventionsCochrane Review of Adherence Interventions
• Tuldra, JAIDS 2000• Study Design
– Usual medical follow up vs education• Psycho educative intervention to implement adherence• Dosing schedule with patients’ input• Phone support
• Study Impact– No effect on adherence– No effect on outcome
Limitations of HAART Adherence StudiesLimitations of HAART Adherence Studies
• Lack of reliable measurements of adherence• Lack of consistent measurements across studies• Assessment of adherence predictors• Small sample size• Variation in study design• Ability to generalize study design• Applicability of other chronic disease studies to HIV • Wide variation in reported results• Limited time of follow up assessments
JAIDS, 2002
Adherence works best when:Adherence works best when:
• Relationship between patient and provider is based on trust• Patient has adequate support• Multidisciplinary healthcare team• Multidisciplinary client centered approach• Approach individually tailored to patient’s needs• Adherence is a process, not a single event