Adherence & HIV

Variability in intervention and standard care impacts treatment outcomes in HAART adherence intervention

trials: A meta-analysis or RCTs

Marijn de BruinWageningen & Maastricht University, the Netherlands

The treatment of HIV• HIV/AIDS & treatment

• High adherence levels important

• Many patients do not achieve or maintain that

• Treatment escalation: viral resistance, opp. infections

Supporting adherence important health care objective

Behavior change interventions

• (Non)Adherence is a behavior

• Causes behavior: ‘determinants’– Knowledge, attitude, planning, forget, lack of support

• Determinants can be influenced by methods / techniques

• When tailored or based on participation more effective

Behavior change interventions

• Active content of interventions:Effective techniques * Important determinants

• HIV: large number of adherence interventions

• Meta-analysis useful to compile research:– Overall effect?– What explains these effects?

• Previous meta’s: small-medium ES, not possible to explain why

Intervention care

50

60

70

80

90

100

1 2 3

50

60

70

80

90

100

1 2 3

Expected: Larger effects caused by more comprehensive interventions

% patients with VL undetectable or adherence >95%Study phase

Intervention care

50

60

70

80

90

100

1 2 3

50

60

70

80

90

100

1 2 3

But that’s funny (part 1)…

But that’s funny… (2)

• Standard care to controls own study more comprehensive than effective interventions

• Possible explanation: SoC different between clinics

Intervention care

Standard care

50

60

70

80

90

100

1 2 3

50

60

70

80

90

100

1 2 3

Variability in standard care…

• Wagner & Kanouse also argued that standard care may vary and impact treatment outcomes (2003, JAIDS)

• If so, intervention effects cannot be accurately interpreted, compared, nor generalized to other settings without controlling for this variability

• Rarely some form of control for SoC content (i.e. active versus passive controls)

Meta 1: Content & effectiveness SC

• Obtain descriptions standard care provided to controls

• Determine the active ingredients

• Examine relation standard care and outcomes

Methods

• Embase, Psycinfo, Medline, trials 1996-2007

• Excl: DOT; focus only on psychiatric, IDU’s, adolescents

• 29 studies included, 95% authors responded

• Standard care checklist, outcomes & other predictors

• Coding manual incl. taxonomy with 41 BCT’s targeting important adherence determinants (adapted from Abraham & Michie, 2008, HP; Bartholomew, Intervention Mapping, 2006).

Determinant # Technique

Knowledge 1 Provide general information

Tailoring

Individualization

2Increase memory & understand.

Awareness 3 Risk communication

Tailoring

4 Self-monitoring of behaviour

5 Self-report of behaviour

6Electronic monitoring of behaviour

7 Reflective listening

8 Delayed feedback of behaviour

Objectively measured

Subjectively measured

9 Direct feedback of behaviour

10 Feedback of clinical outcomes

Social influence

11 Provide info peer behaviour

12 Social comparison peers

13 Norm important other

Attitude 14 Reevaluation, self-evaluation

15 Persuasive communication

Tailoring

16 Reward behavioural progress

17 Reward motivational progress

Self-efficacy

18 Modeling

19 Verbal persuasion

Tailoring

20 Practice, guided practice

21 Plan coping response

Participation

22 Graded tasks, goal setting

Participation

23 Reattribution, ext. attribution

Intention 24 General intention formation Participation

25 Develop medication schedule Tailoring In writing

26 Specific goal setting Participation In writing

27 Review general or specific goals Participation

28 Agree behavioural contract29 Use of social support

Action control 30 Use of cues

31 Self persuasion

Maintenance 32 Goals for maintenance

Participation33 Relapse prevention

ParticipationFacilitation 34 Provide materials

35 Continuous professional support36 Individualize regimen37 Cope with side effects38 Reduce environmental barriers

Example of definition

Determinant: Attitude

16. Reinforcement of behavioural progress:Includes praise and encouragement as well as material rewards,

but the reward/incentive must be explicitly linked to the achievement of specified goals. Also includes use of self-reward strategies.

NB Different from technique #17 in the sense that this technique

reinforces behavioural progress while technique #17 concerns reinforcement of motivational progress.

So does anything happen in the control groups?» ?

DeterminantStandard care activities (coded as techniques)

Coded techniques

Knowledge

Information about HIV, medication and adherence Provide general information

Use of illustrative materials to transfer information Increase memory & understanding

Handing out brochure or written information Additional channel: Brochure

Awareness

Information about consequences of non-adherence Risk communication

Encourage use of 7-day pill box Direct feedback of behavior

Feedback of CD4 & viral load Feedback of clinical outcome

Feedback of MEMS-results* Delayed feedback of behavior

AttitudeInformation about the importance of adherence Persuasive communication

Encourage medication adherence Persuasive communication

Self-efficacy

Encourage storing spare doses in different places Verbal persuasion

Plan ahead for holidays and weekends Plan coping responses

Discuss general barriers and ways to overcome them Plan coping responses

Determine cause non-adherence & generate solutions Plan coping responses

Intention

Develop a medication intake schedule Develop medication schedule

Tailor schedule to patients’ lifestyle Tailor medication schedule

Write down dosing schedule (time, medication, number of pills) Medication schedule in writing

Encourage patients to organize social support Use of social support

Action controlIdentify daily habits and plan intake at these times Use of cues

Encourage use of alarm devices Use of cues

Facilitation

Provide information about side effects & how to deal with them Cope with side effects

Inquire about side-effects & if any, appropriate steps taken Cope with side effects

Delivery of medication at home Provide materials

Social worker helps with housing, unemployment, legal issues Reduce environmental barriers

Design new regimens when regimen is too complex Individualize regimen

Patients with adherence problems return more frequently Tailoring of number of visits

Told to contact health care professional in case of any problems Continuous professional support

Follow-up telephone calls to inquire about difficulties Continuous professional support

DeterminantStandard care activities coded as applications of behavior change techniques

Coded techniques

Knowledge

Information about HIV, medication and adherence

Provide general information

Use of illustrative materials to transfer information

Increase memory & understanding

Handing out brochure or written information Additional channel: Brochure

Awareness

Information about consequences of non-adherence Risk communication

Encourage use of 7-day pill box Direct feedback of behavior

Feedback of CD4 & viral load Feedback of clinical outcome

Feedback of MEMS-results* Delayed feedback of behavior

Attitude

Information about the importance of adherence

Persuasive communication

Encourage medication adherence Persuasive communication

Self-efficacy

Encourage storing spare doses in different places Verbal persuasion

Plan ahead for holidays and weekends Plan coping responses

Discuss general barriers and ways to overcome them Plan coping responses

Determine cause non-adherence & generate solutions Plan coping responses

Intention

Develop a medication intake schedule Develop medication schedule

Tailor schedule to patients’ lifestyle Tailor medication schedule

Write down dosing schedule (time, medication, number of pills)

Medication schedule in writing

Encourage patients to organize social support Use of social support

Action control

Identify daily habits and plan intake at these times Use of cues

Encourage use of alarm devices Use of cues

Facilitation

Provide information about side effects & how to deal with them Cope with side effects

Inquire about side-effects & if any, appropriate steps taken Cope with side effects

Delivery of medication at home Provide materials

Social worker helps with housing, unemployment, legal issues

Reduce environmental barriers

Design new regimens when regimen is too complex Individualize regimen

Patients with adherence problems return more frequently

Tailoring of number of visits

Told to contact health care professional in case of any problems

Continuous professional support

Follow-up telephone calls to inquire about difficulties

Continuous professional support

Summarizing active SoC content

• Large range of techniques and often many per group

• Summarize in quantitative measure SoC capacity:– Standard BCT 1 point– Tailored BCT 2 points– Repeated BCT x2

• Sum score: Standard care capacity

• Reliability standard care tool: Cronbachs alfa .90

Holzemer

Pradier

Levy

Tuldra

Servellen

Knobel

Wagner

Rathbun

Goujard

Weber

Remien

de Bruin

Andrade

Fairley

Wohl

McPherson-Baker

DiIorio

Murphy

0 5 10 15 20 25 30

Figure 1. Variability in standard care capacity

Variability in SoC capacity provided to controls (de Bruin et al., 2009, Health Psychology)

0 5 10 15 20 25 30

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Standard Care Quality

Pro

port

ion

with

Und

etec

tabl

e V

iral L

oad

Relation SoC capacity & viral suppression

Capacity p = .002

Range explains 34% points VL

Ethnicity p=.006

23% lower chance undetectable

Conclusions

• Capacity of adherence support in HIV-clinics varies considerably between settings and is an important predictor of % patients with undetectable viral load

• Meta-analyses that control for SoC variability when examining the effects of interventions more accurate?

Meta-2: Objectives

1. Reliably assess SoC and intervention care capacity

2. Examine relationship with adherence >95% and viral load undetectable

3. Examine whether difference in outcomes intervention and controls is best explained by difference in content (rather than the full content of intervention manuals)

Intervention care

Standard care

50

60

70

80

90

100

1 2 3

50

60

70

80

90

100

1 2 3

Methods• Same search & exclusion procedure

• Randomized controlled trials EU & USA 1996-2009

• Contacted all authors for (30/31):– Intervention & standard care protocols and materials– Characteristics all patients– Viral load and adherence data

• Blinded coders: Kappa .75

Descriptives

• 25/31 RCTs in USA

• 18 treatment experienced patients

• 24 focus specifically on Afr-Am or Hispanic patients

• ½ studies used self-report, other MEMS-caps

• Not all studies measured viral load or adherence; some dropout due to missing SoC or intervention

Including interventions(de Bruin, Archives of Internal Medicine, 2010)

R2 = .8Cap = p<.001

Intervention care

Standard care

50

60

70

80

90

100

1 2 3

50

60

70

80

90

100

1 2 3

“Unique intervention capacity”

R2 = .78Cap VL p = .02Cap ad p <.01

Checks

• Deleting lower quality studies did not affect results• No evidence of publication bias

Strongest additional predictors• Non-caucasian 27% lower chance undetectable• MEMS 50% point lower adherence than self-reports• Methodological checks (e.g. dropout, intensity)

Excluding n.s. predictors did not affect the outcomes

And

rade

Kno

bel

Col

lier

Rig

sby

Gou

jard

Jone

s200

7

Dilo

rio20

08

Pra

dier

Woh

l

Hol

zem

er

Java

nbak

ht

Rat

hbun

Tul

dra

Koe

nig

Ser

velle

n

Sm

ith

Mur

phy2

002

Rem

ien

Rat

e D

iffer

ence

And

rade

Kno

bel

Col

lier

Rig

sby

Gou

jard

Jone

s200

7

Dilo

rio20

08

Pra

dier

Woh

l

Hol

zem

er

Java

nbak

ht

Rat

hbun

Tul

dra

Koe

nig

Ser

velle

n

Sm

ith

Mur

phy2

002

Rem

ien

Rat

e D

iffer

ence

00.

050.

10.

150.

20.

250.

30.

350.

4

Expected Rate Differences under Difference Levels of Standard Care

Expected ratedifference forRemien under:

Low SCQ

Medium SCQ

High SCQ

Conclusions (1)• Capacity of qualitatively sound adherence care crucial for

treatment success (40-50% undetectable VL)

• SoC often suboptimal, but content high quality adherence care known

• Limited evidence of (cost)effectiveness interventions on top of “current best practice”: Implement?

• Additional predictors, e.g. ethnicity, adherence measurement

Conclusions (2)Without accurate SoC reports, intervention effects cannot beinterpreted What was the unique content?compared Different testing conditions?generalized How does SoC map onto other settings?

• Replicate findings• Future meta’s should control for SoC variability• Intervention & SoC reports should improve

• Future meta’s should control for SoC variability• Intervention and SoC reports should improve

Questions raised…

• What does this mean for previous meta’s?

• And for interventions already published?

• And for health care based on this work?

Marijn.debruin@wur.nlWageningen University, the Netherlands