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