1. 1 Impact of Electronic Drug Monitoring Feedback on Adherence to Antiretroviral Therapy April 6, 2009 Lora Sabin Center for International Health and Development Boston University

2. China Adherence For Life (AFL) study collaborators Boston University SPH Lora Sabin, MA, PhDLora Sabin, MA, PhD Christopher J. Gill, MS, MDChristopher J. Gill, MS, MD Mary B. DeSilva, MS, ScDMary B. DeSilva, MS, ScD Davidson H. Hamer, MDDavidson H. Hamer, MD Tufts-New England Medical Center Ira Wilson, MS MDIra Wilson, MS MD Funding provided by: USAID, WHO/Beijing, US CDC Additional acknowledgments: Don Thea, Jon Simon, Deirdre Pierotti, Mini Singh, Anna Knapp, James Chen, Wan- ju Wu, Guo Jianhua, Matt Bobo, Ahmar Hashmi, and Jordan Tuchman Ditan Hospital, Beijing Xu Keyi, MDXu Keyi, MD Dali Second People’s Hospital, Dali Zhang Jianbo, MDZhang Jianbo, MD Horizon Research Group, Beijing Yuan Yue, MA, PhDYuan Yue, MA, PhD Fan Wen, MAFan Wen, MA Li Tao, MALi Tao, MA

3. 3 Background China is rapidly scaling up ART, but treatment programs are at an early stage:China is rapidly scaling up ART, but treatment programs are at an early stage: Little is known about levels of adherence, particularly among IDUs and former IDUsLittle is known about levels of adherence, particularly among IDUs and former IDUs Little is understood about how to improve adherenceLittle is understood about how to improve adherence Drug resistance is rising, and there are fears about the cost and availability of 2 nd and 3 rd line regimensDrug resistance is rising, and there are fears about the cost and availability of 2 nd and 3 rd line regimens As in other countries, there is an urgent need for interventions that are effective in improving adherence among HIV-positive patientsAs in other countries, there is an urgent need for interventions that are effective in improving adherence among HIV-positive patients

4. The relationship between ART adherence and HIV outcomes was deduced using electronic drug monitors (EDM) EDM pill bottles have an embedded microchip in the capEDM pill bottles have an embedded microchip in the cap –Time/date stamps each bottle opening –Surrogate marker for adherence Comparative studies show that EDM are by far the best measure of adherence available.Comparative studies show that EDM are by far the best measure of adherence available.

5. STUDY QUESTION: Can we improve adherence to ART using Electronic Drug Monitor (EDM) feedback?

6. 6 Overview of AFL (Control) Continued passive observation (Intervention) Active EDM feedback Adherence observed prospectively via EDM, relationship between barriers and actual adherence, clinical outcomes measured Phase I 6 months Phase II 6 months Phase III 6 months Qualitative investigations on what patients/doctors in Dali view as key barriers to adherence Randomized controlled trial to determine effectiveness of EDM feedback strategy N=80 Patients enrolled N=68 Patients randomized

7. Study site, Dali, Yunnan Province Yunnan province Dali

8. Study population HIV epidemic driven by injectable drug useHIV epidemic driven by injectable drug use Lesser contribution from commercial sex workLesser contribution from commercial sex work Minimal spread into larger populationMinimal spread into larger population

9. AFL Study objectives 1. Primary Objective  To determine effect of EDM feedback on adherence rates 2. Secondary Objectives  To determine effect of EDM feedback on CD4-cell counts and undetectable viral loads (UDVL) The study was powered to detect a 15% difference in adherence rates, as assessed by EDM

10. Randomization Procedure Block stratified randomizationBlock stratified randomization At end of Phase I, patients stratified by ‘high’ or ‘low’ adherenceAt end of Phase I, patients stratified by ‘high’ or ‘low’ adherence ≥95% = ‘high adherence’≥95% = ‘high adherence’ <95% = ‘low adherence’<95% = ‘low adherence’ Based on average adherence during the 5 months prior to randomizationBased on average adherence during the 5 months prior to randomization Equal numbers of patients allocated from within each adherence stratumEqual numbers of patients allocated from within each adherence stratum Ensured balanced allocation at start of interventionEnsured balanced allocation at start of intervention

11. What happened in intervention group? EDM data reviewed at each monthly study visitEDM data reviewed at each monthly study visit Patients with <95% adherence by EDM in previous month flagged for “additional adherence counseling”Patients with <95% adherence by EDM in previous month flagged for “additional adherence counseling” EDM report given to doctor and patient at each visitEDM report given to doctor and patient at each visit % doses taken% doses taken % on time% on time Histogram readoutHistogram readout Additional counseling had no fixed scriptAdditional counseling had no fixed script involved a conversation between doctor and patient in which doctor asked about problems or challenges, referring to EDM print-outinvolved a conversation between doctor and patient in which doctor asked about problems or challenges, referring to EDM print-out

12. What happened in control group? Self-report data reviewed at each monthly visitSelf-report data reviewed at each monthly visit EDM data not provided to doctor/patientEDM data not provided to doctor/patient Patients with <95% adherence by self report in previous month flagged for “additional adherence counseling”Patients with <95% adherence by self report in previous month flagged for “additional adherence counseling” Like intervention arm, additional counseling involved a conversation in which doctor asked about problems or challenges faced, referring to patient’s self-reportLike intervention arm, additional counseling involved a conversation in which doctor asked about problems or challenges faced, referring to patient’s self-report

13. Definition of Primary Outcome Metric Composite EDM measure includes proportion taken and timing of doses: # doses taken +/- 1 hour of scheduled time # prescribed doses

14. Clinical measures CD4-cell count Undetectable Viral load (UDVL) (Using RT PCR: <400 copies/ml = “undetectable”

15. RESULTS

16. 16 Patient Characteristics at randomization (Mo. 6) * Statistically significant at the p<0.01 level

17. 17 Patient Characteristics at randomization (Mo. 6) ** basis for block randomization procedure

18. *p<0.05** p<0.01 At Month 6, no significant differences between intervention and control groups At Month 12, large increase in adherence in intervention arm; no significant increase in control arm. Point Adherence at Months 6 and 12

19. ** p<0.01 At Month 6, no significant differences between intervention and control groups (in Months 1-6 adherence) Large increase in adherence in Months 7-12 in intervention arm; no significant increase in control arm. Mean adherence over time, periods 1 and 2

20. Achievement of mean adherence ≥95% throughout Months 7-12 Intervention n/N (%) Control 23/31 (74) 11/33 (33) RR = 2.23 (95% CI 1.3-3.8) ***p=0.001

21. Composite Adherence by group and time

22. Clinical outcomes: Changes in CD4-cell counts between months 6 and 12 Intervention No. (%) Control Proportion with CD4 increase, months 6-12 22/31(71%)15/31(48%) RR 1.5 (1.0-2.2) p=0.072 Mean change in CD4 (x1000 cells/ml) + 90 - 9 p=0.020 Note: regarding UDVL: little change from Month 6

23. Patient-level EDM view: A near perfect patient profile

24. Patient-level EDM view: A patient with poor adherence

25. Patient-level EDM view: A patient with improved adherence 6 months Pre-intervention phase Intervention phase

26. Main Findings EDM feedback improved ART adherence EDM feedback improved ART adherence Adherence rise was prompt and sustainedAdherence rise was prompt and sustained Intervention arm: adherence improvedIntervention arm: adherence improved Control arm: adherence stayed steady with a falling trendControl arm: adherence stayed steady with a falling trend Effect seen in both Month 6 v. Month 12 point comparisons and in pre-intervention v intervention phase comparisonsEffect seen in both Month 6 v. Month 12 point comparisons and in pre-intervention v intervention phase comparisons Patients more likely to achieve ≥95% adherencePatients more likely to achieve ≥95% adherence EDM feedback improved clinical outcomes EDM feedback improved clinical outcomes CD4-cell counts rose significantlyCD4-cell counts rose significantly Trend towards higher proportion of rising CD4s among intervention armTrend towards higher proportion of rising CD4s among intervention arm EDM feedback is a promising intervention – it warrants further evaluation in other populations EDM feedback is a promising intervention – it warrants further evaluation in other populations

27. Thank you for your attention Any questions?