Improving Adherence in HIV Treatment with Once-Daily Therapies
ADHERENCE Patrick Desmet HIV / Therapycounselor.
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Transcript of ADHERENCE Patrick Desmet HIV / Therapycounselor.
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ADHERENCE
Patrick Desmet HIV / Therapycounselor
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0
5
10
15
20
25
30
35
40
1995 1996 1997 1998 1999 2000 2001
Dea
ths
per
100
Per
son
-Yea
rs
0
25
50
75
100
DEATHS
USE OF HAART
Mortality vs HAART UtilizationP
atient-Days o
n HA
AR
T, %
PALELLA, NEJM 1998
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WAC, Geneva 1998
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The medication adherence is the ability of the patient to be involved in:choosing , starting, managing and maintaining a given therapeutic combination regimen to control viral replication and improve the immune function. Jane M.Simoni Ph D
Definition Adherence
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Objective: Effect of baseline CD4-count and adherence to HAART on survival rate
ADHERENCE vs. SURVIVAL
Methods : • 1422 HIV patients• 2-6 years follow-up• Adherence : first 48 weeks pharmacy refills• 2 categories:>75% and >95% adherent refills• CD4 ranges: >200-349 cells or ≥350 cells
Evan Wood 2003 / Annals of Internal Medicine
ConclusionAdherent=SIMILAR MORTALITY RATES
CD4: 200-349 and greater (p > 0.2)
(p=0.004)Non-Adherent = increased mortality rateCD4 range: >200-349
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ADHERENCE vs. SURVIVAL
CONCLUSION:
In HIV-infected individuals, adherence, rather than when therapy is initiated above a CD4-count of 200 cells may be the most important determinant of survival
Evan Wood 2003 / Annals of Internal Medicine
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How Much Adherence Required
Adapted from: Paterson DL et al. Ann Intern Med 2000;133: 21-30
Mean adherence rate
Relationship of adherence (measured by MEMS® 81 patients / 45397 doses /
6 months of FU ) to virologic success
78
4533
2918
0
25
50
75
100
>95% 90%-95% 80%-90% 70%-80% <70%
Pat
ien
ts R
eac
hin
g U
nd
etec
tab
le
HIV
RN
A L
OQ
400
(%
)
P = <0.001
Greatest danger zone for developing resistance
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Adherence levels over time impact on virological response
Adherence levels at 6 months and virological response
0
10
20
30
40
50
60
Per
cen
tag
e o
f p
atie
nts
<
200
cop
ies/
ml
90-95%
52%
70-89%
35%
40-69%
20%
<40%
18%
N=3004 / 69 centers
Casado JL et al. 42nd ICAAC, San Diego CA, September 2002. Abs H-1707
Level of adherence
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ADHERENCE
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Health Care Team
MULTIDISCIPLINARY TEAM EFFORT
HIV-CARE TEAM COMMUNITY-CARE•HIV-SPECIALIST
•NURSE / THERAPY •COUNSELOR •SOCIAL WORKER•PSYCHOLOGIST•PHARMACIST•DIETICIAN
•GP•VOLUNTEERS•HOME BASED CARE•PATIENT ORGANISATIONS
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HEALTHCARE FACTORS
• STAFF TRAINING
• INSUFFICIENT STAFF & SPACE for COUNSELLING
• CONFIDENTIALITY
• POOR ORGANIZATION OF DAILY CARE
•AUTHORITARIAN AND JUDGEMENTAL ATTITUDE
• CONFLICTING PATIENT-INFORMATION (EDUCATION)
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PATIENT FACTORS
PATIENT
EMPOWERMENT
BASIC KNOWLEDGE
SKILLS &MOTIVATION
HEALTHBELIEFS &CULTURAL /SOCIO-ECONOMICSTATUS
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BASIC KNOWLEDGE
WHAT ? WHEN ? WHY ?
•CD4 / CD4 % / VL
•EXPECTATIONS :GOLDEN STANDARD
•ADHERENCE
•RISKS & BENEFITS of EARLY / DELAYED ART
• ADHERENCE
• LIFELONG TREATMENT & ART RESTRICTIONS
•HIV vs. AIDS
• ART / ACTION
PATIENT FACTORS
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HEALTH BELIEFS & FEARS
•Denial HIV- status
•Negative beliefs (expectation of benefit ART)
•Fear of Short or Longterm - Side Effects
•Lack off trust towards Health-Care team
PATIENT FACTORS
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Cultural and Socio-economic Status
•Drug and Alcohol use
•Fear of Disclosure : ARV > trigger HIV-Status
•Welfare status: housing, financial support…
•Stigmatisation : cultural / religious beliefs
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MOTIVATION
ESTABLISH : READINESS COMMITMENT
ASYMPTOMATIC vs. SYMPTOMATIC
MOTIVATION MOTIVATION
• Preventive Measures
• ART-SE Distress ART Stop = SE Relief
• Reinforce the Necessity
• OI-status, Pill Burden, Drug-drug Interactions
LONG-TERM TREATMENT
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TREATMENT FACTORS
• CONCOMITANT /ALTERNATIVE MEDICINE
• DRUG TOXICITIES: SHORT AND LONGTERM SE
• COMPLEX REGIMEN / PILL BURDEN
• DOSING FREQUENCY / DRUG INTERACTIONS
• DIETARY RESTRICTIONS
• LOGISTICAL : APPROVALS / AVAILABILITY OF DRUGS
• ACCUMULATIVE TREATMENT CHANGES
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What’s the VirologicImpact of Pill Burden?
Number of Antiretroviral Pills Prescribed Per Day
Bartlett. 13th IAC; 2000; Durban. Abstract 4998.
80
60
40
20
05 10 15 20
HIV
RN
A
50 a
t 48
wee
ks
PI
NRTI
NNRTI
(r = –0.57, P = .0085)
Size of symbol is directly proportional to weight of the data point in the analysis.
100Meta-analysis of 22 clinical trials / 3257 patients first line HAART
48 weeks of follow up
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* Indicates group “Taking all medication on time according to food restriction” not assessedNieuwkerk PT et al. Arch Int Med 2001,161: 1962-1968
As Regimen Complexity Increases Adherence Rates Decrease
Taking all medications
Taking all medications on time
0
20
40
60
80
IDV + NRTIs NFV + NRTIs RTV/SQV +NRTIs
NVP + NRTIs
Pat
ien
ts (
%)
100
Taking all medications on time according to food restrictions
*
N=224
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SIMPLIFIED
PILL BURDEN FREQUENCY DIET RESTRICTIONS
AVOIDSUB-OPTIMALADHERENCE
SIMPLIFYFREQUENCY
QD+BID = COMPLEXITY
PILL BURDEN > 6 PILLS
SEPARATE TIMING = DIET
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Frequency of dosing and forgetting medication
0
20
40
60
80
100
% o
f pat
ients
eve
r fo
rget
ting t
o
take
HIV
med
icat
ion
Once dailyTwice daily3 times daily>3 times daily
Moyle G Moyle G et alet al. 6th ICDTHI, Glasgow, UK, 17-21 November 2002. Poster 99. 6th ICDTHI, Glasgow, UK, 17-21 November 2002. Poster 99
40%
N=504 across Europe
63% 66% 71%
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Why do Patients Miss Doses?
Adapted from: Gifford AL et al. JAIDS 2000; 23: 386-395
Reasons given for missing antiretroviral doses
(structured questionnaire)
possible interventions
simplify dosing schedule
decrease pill burden
other
%
n=13352
46
45
27
20
20
19
19
18
17
17
16
14
13
10
9
0 10 20 30 40 50 60
Too busy/simply forgot
Away from home
Change in daily routine
Felt depressed/overwhelmed
Took drug holiday/medication break
Ran out of medication
Too many pills
Worried about becoming 'immune'
Felt drug was too toxic
Wanted to avoid side effects
Didn't want others to notice
Reminder of HIV infection
Confused about dosage direction
Didn't think it was improving health
To make it last longer
Were told the medicine is no good
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1
10
100
1000
10000L
og
co
nce
ntr
atio
n (
ng
/mL
)
day 1 day 2 day 3 day 4 day 5
dose dose dose missmiss dose
EC50Even 48 hours post-dose, plasma levels remain above EC50
Half life: >12 hours
Examples: EFV, TDF, ddI, Atazanavir
The Weakest Link !!!
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MEASUREMENT
• DOT
• PHARMACY BASED RECORDS
• CLINICAL JUDGEMENT
• SELF REPORT
• BIOCHEMICAL PARAMETERS
• ELECTRONIC EVENT MONITORING (MEMS®)
HOW ?
• PILL COUNTS
• PLASMA LEVELS / TDM
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Direct Observed Therapy
PRO CONTRA
• May theoretically be justified:> 100 % levels of adherence
• Labor intensive: >only for QD-BID dosing > can be used for observational limited time
• Expensive
• Restricted to institutional setting: > targetted patient population prisons, etc..
• Confidentiality
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PRISONERSPRISONERS
00
2020
4040
6060
8080
100100
44 88 1616 2424 4848 6464 7272
Weeks on therapyWeeks on therapy
HIV
RN
A <
400,
%
HIV
RN
A <
400,
%
SELF ADMINISTERED THERAPYSELF ADMINISTERED THERAPYVS.
M.Fishl CROI 2001
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PRO CONTRA
Clinician/Nurses-Estimated Adherence
• Open-ended questions• Slightly better than a coin
toss !• Paterson et al.: prediction
>80% adherence
physician 41% incorrect
nurses 30% incorrect
White coat-effect !?
• Cheap
•Phrasing Questions in specific terms > dosing > timing > anticipating > diet
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Adherence = phrasing questions in specific terms
ex. Timing : How and When did your demanding job influence your ARV- timing schedule? Could you combine your Kaletra with your dinner?
ex. Anticipating : Seeing your parents this week-end, how did you to plan ahaed your ARV’s in order not to disclose your HIV-status?
Adherence= avoid open-ended questions
ex. Looking at your labresults I suppose you didn’thave any problems taking your medications?
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VIRAL LOAD : Standard assay> can be objective if combined with patient self-reports
BIOCHEMICAL PARAMETERS
CD4 / CD4% : Ojective measure , good correlation
MCV- increase reflects AZT-intake, poor correlation
Genotypic Resistance testing: marker of non-adherence
! Only absolute non-adherent patients !Assay misleading if patient is no longer on drug> 3TC failing patients still susceptible for the RT184 mutation
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PRO CONTRA
Pill Counts
• Cheap• Useful adjunct to
self-report
• Overestimates adherence– “Pill dumping” > hospital
flowerbeds
• Time consuming• Rather in research setting>
structured dosing schedules• Counsellor = medication
monitor > threatening
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PRO CONTRA
Pharmacy Records / Refills
• Cheap• Useful adjunct to
self-report
• 1 patient vs. many pharmacies
• Refilling doesn’t mean drugtaking
• Patient may have different sources of medications: free samples, pill sharing,
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ADHERENCE vs. PHARMACY REFILLS
Hogg et al.7th CROI 2000/abs73.
Objective : HIV-disease progression / AIDS vs. Adherence
Methods : • 950 patients ARV naive• (85% PI and 15%NNRTI) + 2NRTI• Median follow-up 13 months• Pharmacy based records, refills
Conclusion For each 10% decline in adherence
16% increase in mortality
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PRO CONTRA
Self-Report
• Cheap• Correlated with
virologic outcomes.
• Overestimates adherence
• Accuracy can be improved by gathering and averaging information over time
• Diaries: easily neglected and lost…
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Electronic Event Monitoring (MEMS®)
6 10 14 18 22 26 30 4 8 12 16 20 24 28
04:00
08:00
12:00
16:00
20:00
24:00
September October
Tim
e
UZ LeuvenFabienne Dobbels
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Electronic Monitoring (MEMS®)
• Best correlation with virologic outcomes
• Data is available in a computer accessible format
• Allows more detailed view of the dynamics of drug intake.
• Expensive : 125€ /drug/patient
• Not for routine daily practice > limited to research settings
> Poor patient acceptance
• Not infallible (patients can open bottle and not take pill)
PRO CONTRA
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CONCLUSION
NO DECISIVE TOOL and/or METHOD TO MEASURE
PATIENT SELF - EFFICACY
ADHERENCE
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Flow Chart Counseling New HIV+
TRUST KNOWLEDGELIFESTYLEPotential ADHERENCE and ARV-BARRIERS
OPTIMISING HAART
PEOPLES LIVES = VARIABLE BEHAVIOR
IMPACT from ENVIRONMENT SOCIAL FACTORS NEW DIAGNOSES
DYNAMIC MONITORING
3 STEP APPROACH = a stepwise informationflow
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Counseltopics
• Sec.Prevention:Safe sex,blood
•HIV virus basics
•Social:partner,disclosure
•CD4 & VL-interpretation
•Side-effects: short and long-term
•Video
Counseltopic(s): naive patients
•Evaluation 2 ARV proposals
Lifestyle:Diet, work, co-medication…
Potential Adherence and Therapy barriers
Social status check !
Drug specific Side effects
•Initiate Dummy Run
•ARV support
•Adherence: 4 markers
• Resistance
2 visits
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Counseltopics
•Drugplanning: optimizing drugintake, identify ARV-reminders, ARV-storage, food recommendations….
•Patient rehearses drugplanning and potential SE
•Drug specific SEffects
• Supportive Tools
Counseltopics
•Telephone call patient / counselor
•Anticipate SEffects cf Dr.
•Adherence check:
= Timing , dosing, diet,anticipation, ARV_storage.
•Reasons for non-adherence
Initiation Haart and follow- up
READINESSCOMMITMENT
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Medication schedule
Medication Frequ. Hours Nutrition Remarks
1 co Retrovir® 300 mg 2x/day
1 caps Videx® EC 400 mg 1x/day On an empty stomach = take 1 hour beforea meal or 2 hours after a meal
1 caps Stocrin® 600mg 1x/day Do not take after a fatty meal
4 caps Kaletra® 133.3/33.3mg 2x/day Store bottle at room temperature for max.42 daysStore reserve in refrigerator
UZ Leuven
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Pillbox and reminder system
UZ Leuven
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Vibrating alarms, watches,
cell-phone alarm, SMS
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ADHERENCE COUNSELLING
MULTIDISCIPLINARY TEAM EFFORT
NEGOTIATIONINFORMATION EDUCATION
BEFORE, DURING and AFTER START of ART