Impact of Electronic Drug Monitoring Feedback on Adherence to Antiretroviral Therapy

April 6, 2009

Lora Sabin Center for International Health and Development Boston University 1

China Adherence For Life (AFL) study collaborators

•

Ditan Hospital, Beijing

Xu Keyi, MD • • • •

Boston University SPH

Lora Sabin, MA, PhD Christopher J. Gill, MS, MD Mary B. DeSilva, MS, ScD Davidson H. Hamer, MD •

Dali Second People’s Hospital, Dali

Zhang Jianbo, MD •

Tufts-New England Medical Center

Ira Wilson, MS MD • • •

Horizon Research Group, Beijing

Yuan Yue, MA, PhD Fan Wen, MA Li Tao, MA

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

Background

• 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 IDUs • Little 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 regimens • As in other countries, there is an urgent need for interventions that are effective in improving adherence among HIV-positive patients 3

The relationship between ART adherence and HIV outcomes was deduced using electronic drug monitors (EDM)

• • EDM 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.

STUDY QUESTION:

Can we improve adherence to ART using Electronic Drug Monitor (EDM) feedback?

Overview of AFL

N=80 Patients enrolled N=68 Patients randomized (Control) Continued passive observation (Intervention) Active EDM feedback 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 Adherence observed prospectively via EDM, relationship between barriers and actual adherence, clinical outcomes measured Randomized controlled trial to determine effectiveness of EDM feedback strategy 6

Study site, Dali, Yunnan Province

Dali

Yunnan province

Study population

• • HIV epidemic driven by injectable drug use Lesser contribution from commercial sex work • Minimal spread into larger population

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

Randomization Procedure

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

What happened in intervention group?

•

EDM data

reviewed at each monthly study visit • Patients with <95% adherence

by EDM in previous month

flagged for “additional adherence counseling” • EDM report given to doctor and patient at each visit • • • % doses taken % on time Histogram readout • Additional counseling had no fixed script • involved a conversation between doctor and patient in which doctor asked about problems or challenges,

referring to EDM print-out

What happened in control group?

•

Self-report data

reviewed at each monthly visit • EDM data not provided to doctor/patient • 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-report

Definition of Primary Outcome Metric

Composite EDM measure

includes proportion taken and timing of doses: # doses taken +/- 1 hour of scheduled time # prescribed doses

Clinical measures

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

RESULTS

Patient Characteristics at randomization (Mo. 6) Characteristic

Gender Male Female Age (Mean, SD) Education* Elementary Junior high Senior high/technical school Marital status Single Married Ethnic background Han Chinese Bai Other Household size Employment status Currently employed Currently unemployed

Intervention Number (%) Mean (SD)

25 (74) 9 (26) 7 (21) 17 (50) 10 (29) 15 (44) 19 (56) 18 (53) 14 (41) 2 (6) 10 (31) 22 (69) 36.1 (8.3) 4.2 (1.5) * Statistically significant at the p<0.01 level

Control Number (%) Mean (SD)

25 (74) 9 (26) 13 (38) 20 (59) 1 (3) 16 (47) 18 (53) 15 (44) 17 (50) 2 (6) 12 (37) 20 (63) 35.1 (8.0) 4.5 (1.4) 16

Patient Characteristics at randomization (Mo. 6) Characteristic

Heroin use in previous 3 mos Yes No Depression (Beck's, continuous) Depression (Beck's, binary) Yes No CD4, Month 6 (continuous) UDVL, Month 6 (yes) Mean adherence, Months 0-5** High (>= 95%) Low (<95%)

Intervention Number (%)

4 (12) 30 (88) 6 (18) 27 (82) 30 (88.2) 16 (47) 18 (53) ** basis for block randomization procedure

Mean (SD)

9.8 (3.6) 297 (145)

Control Number (%) Mean (SD)

5 (15) 29 (85) 10 (30) 23 (70) 28 (87.5) 17 (50) 17 (50) 10.2 (4.0) 357 (196) 17

Point Adherence at Months 6 and 12

*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.

Mean adherence over time, periods 1 and 2

** 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.

Achievement of mean adherence ≥95% throughout Months 7-12

Intervention n/N (%) 23/31 (74) Control n/N (%) 11/33 (33) RR = 2.23

(95% CI 1.3-3.8) ***p=0.001

Composite Adherence by group and time

100% 95% 90% 85% 80% 75% 70% 65% 60% 55% 50% 1 2 3 4 5 6

Month

7 Low adherers, intervention group Low adherers, control group High adherers, intervention group High adherers, control group 8 9 10 11 12

Clinical outcomes: Changes in CD4-cell counts between months 6 and 12

Intervention No. (%) Proportion with CD4 increase, months 6-12 22/31 (71%) RR 1.5 (1.0-2.2) p=0.072

Mean change in CD4 (x1000 cells/ml) p=0.020

Note: regarding UDVL: little change from Month 6 + 90 Control No. (%) 15/31 (48%) - 9

Patient-level EDM view: A near perfect patient profile

Patient-level EDM view: A patient with poor adherence

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

Main Findings

• EDM feedback improved ART adherence • • Adherence rise was prompt and sustained • • • Intervention arm: adherence improved Control 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 comparisons Patients more likely to achieve ≥95% adherence • EDM feedback improved clinical outcomes • • CD4-cell counts rose significantly Trend towards higher proportion of rising CD4s among intervention arm • EDM feedback is a promising intervention – it warrants further evaluation in other populations

Thank you for your attention Any questions?