Adherence & HIV

1. Adherence & HIV Variability in intervention and standard care impacts treatment outcomes in HAART adherence intervention trials: A meta-analysis or RCTs Marijn de Bruin Wageningen & Maastricht University, the Netherlands

2. 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

3. 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

4. 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

5. Expected: Larger effects caused by more comprehensive interventions Intervention care % patients with VL undetectable oradherence >95% Study phase

6. But that’s funny (part 1)… Intervention care

7. But that’s funny… (2) • Standard care to controls own study more comprehensive than effective interventions • Possible explanation: SoC different between clinics

8. Intervention care Standard care

9. 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)

10. Meta 1: Content & effectiveness SC • Obtain descriptions standard care provided to controls • Determine the active ingredients • Examine relation standard care and outcomes

11. 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).

15. 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.

16. So does anything happen in the control groups? • ?

20. 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

21. Murphy DiIorio McPherson-Baker Wohl Fairley Andrade de Bruin Remien Weber Goujard Rathbun Wagner Knobel Servellen Tuldra Levy Pradier Holzemer 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)

22. Relation SoC capacity & viral suppression Capacity p = .002 Range explains 34% points VL Ethnicity p=.006 23% lower chance undetectable

23. 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?

24. Meta-2: Objectives • Reliably assess SoC and intervention care capacity • Examine relationship with adherence >95% and viral load undetectable • Examine whether difference in outcomes intervention and controls is best explained by difference in content (rather than the full content of intervention manuals)

25. Intervention care Standard care

26. 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

27. 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

29. Including interventions(de Bruin, Archives of Internal Medicine, 2010) R2 = .8 Cap = p<.001 Δ Δ

30. Intervention care Standard care

31. “Unique intervention capacity” R2 = .78 Cap VL p = .02 Cap ad p <.01

32. 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

34. 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

35. Conclusions (2) Without accurate SoC reports, intervention effects cannot be interpreted  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

36. 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.nl Wageningen University, the Netherlands