Update on Individualized Texting for Adherence Building (iTAB): Lessons for Implementation

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AIDS CLINICAL ROUNDS

HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO

Update on Individualized Texting for

Adherence Building (iTAB): Lessons for

Implementation

David J. Moore, Ph.D.

University of California, San Diego

Department of Psychiatry


Brief Outline

Texting and adherence in HIV

iTAB System

Results from completed/ongoing studies

» iTAB-B: HIV+ with bipolar disorder

» iTAB-M: HIV+ with active meth use

» CCTG 595: HIV- taking PrEP

Conclusions


Texting Improves ART Adherence

SMS (texting) interventions for improving ART adherence

show promise

In a 2012 Cochrane report, two RCTs shown to be

efficacious for ART improvement:

» 1X week text over a 12-month interval decreased non-adherence

and virologic failure (Lester et al., 2010)

» 1X week versus 1X day text messages; at 48-weeks, weekly

messages were more likely to reduce non-adherence and

treatment interruptions (Pop-Eleches et al., 2011)

Optimal texting systems for adherence improvement in

difficult-to-treat populations in US still evolving

Horvath et al., Cochran Report, 2012; Lester et al., 2010; Pop-Eleches et al. 2011


Personalized iTAB intervention

iTAB -- Pts create personalized med reminder texts:

• Description of medications

• Personalized reminder stems (e.g., “remember

to take your meds, they make you healthy”)

• Preferred name

• Ideal time for reminders each day by med

Both iTAB and CTRL received:

• Adherence psychoeducation (~30 min)

• A daily text message asking about mood

• Process of medication reminder creation

• Sentinel med for MEMS: ARV: Mostly combo

medication; PSY: Primary mood stabilizer


Example of Customizable iTAB System


Example of Customizable iTAB System


iTAB Decision Tree

Other iTAB components:

• 3 consecutive days of non-

responses get a

“noncompliance” text

• 5 consecutive days of non-

responses, call from RA

• Adherence Targets:“Ur

current adherence: xx%.

Adhr when u take ur next

dose: xx% (x/x doses)”

• Personalized Reinforcer


iTAB Studies

iTAB-B iTAB-M CCTG 595

Group HIV+ Bipolar HIV+ Meth HIV-

Design RCT (n=50) RCT (n=75) RCT (n=400)

Status Enrolled Enrolling (n=23) Start 12/1

Duration 4 weeks 6 weeks 48 weeks

Referrals N/A Please!619-543-

5000

619-543-5011


iTAB in HIV+ with Bipolar Disorder

(iTAB-B)


iTAB-B Study Flow

Assessed for eligibility (n=62)

Allocated to iTab intervention

(n=30)

Lost to follow up

(n=2)

Analyzed (n=25)

• Lost MEMS (n=3)

Allocated to CTRL intervention

(n=28)

Lost to follow up

(n=2)

Analyzed (n=25)

• Lost MEMS (n=1))

Excluded (n=4)

• Not meeting inclusion criteria (n=2)

• Declined to participate (n=1)

• Withdrawn (n=1)

Enrollment

Randomized (n=58)

Allocation

Follow-up

Analysis


Example iTAB-B Intervention Stems

» Celebrate Health

• Stay healthy! It’s time 2

take ur meds, pls take ur…

» Time and Focus

• It’s pill time! Take ur…

» Control Disease

• Taking ur meds helps

control ur disease. Rmber

2 take ur…

» Empowering

• It’s med time, only u can

control this. Rmber 2

take ur…

» Importance of Adherence

• Adherence is impt. Pls

take ur…

Stems of personal reminder messages reflect different themes:


Demographics

CTRL (n=25) ITAB (n=25) P-value

Age 45.9 (10.2) 48.4 (9.2) 0.36

Education 13.0 (3.1) 13.3 (2.2) 0.67

Ethnicity (% White) 44.0 64.0 0.26

Sex (% Male) 84.0 92.0 0.67

Global Deficit Score 0.7 (0.7) 0.6 (0.6) 0.68


Psychiatric Characteristics


Lifetime Substance

Diagnosis,% 87.5 68.0 0.10

Current Substance

Diagnosis, % 4.2 4.0 0.98

Euthymic during the

prior month, % 64.0 64.0 0.62

Beck Depression

Inventory–II 18.0 (10.6) 17.0 (12.6) 0.77

Young Mania Rating

Scale 5.2 (4.5) 6.4 (7.6) 0.49

GAF 67.3 (10.9) 68.0 (10.0) 0.82


Medical Characteristics


Current CD4 Count 655.8 (324.2) 603.4 (392.8) 0.67

Nadir CD4 Count 225.7 (153.1) 281.2 (258.2) 0.44

HIV RNA Detectable, % 8.0 24.0 0.12

AIDS Status, % 60.9 70.0 0.75


Medication Characteristics


Self report % ARV doses

taken (past month) 87.9 (16.8) 96.0 (7.2) 0.10

Self report % PSY doses

taken (past month) 89.0 (19.2) 94.1 (9.9) 0.41

Total No. of ARVs 6.9 (4.5) 7.1 (4.5) 0.75

Total No. of rx doses, ARV 42.7 (13.8) 41.5 (14.2) 0.61

Total No. of rx doses, PSY 47.7 (24.1) 44.7 (19.0) 0.57


Overall MEMS Adherence by Group

0

10

20

30

40

50

60

70

80

90

100

ARV PSY

ME

MS

% o

f P

rescri

bed

Do

eses

Taken

CTRL

iTAB

N=2

5

N=25

p = 0.28 p = 0.94

N=25 N=25


Overall MEMS % On Schedule by Group

p = 0.25 p = 0.89

0

10

20

30

40

50

60

70

80

90

ARV PSY

CTRL

iTAB

N=25 N=25 N=25 N=25


Time from Target Dose by Group

p = 0.03 p = 0.34

Cohen’s d = -0.33 Cohen’s d = 0.04

N=25 N=25 N=25 N=25


Adherence & Mania Ratings

YMRS total

F (1, 49) = 6.774

p = 0.012

YMRS total

F (1, 46) = 2.705

p = 0.107


Frequency of Stems Selected

# Stem # Stem

1 Ur health is impt, rmber 2 take ur meds. Take ur [med] now. 10 Adherence is impt. Pls take ur [med] now.

2 Stay healthy! It's time 2 take ur meds, pls take ur [med] now. 11 2 help keep u feeling good, rmber 2 take ur [med] now.

3 No matter what else is going on, it's impt 2 take ur [med] now. 12 Ur meds are important. It's time for ur next dose of ur [med] now.

4 It's med time! Pls take ur [med] now. 13 Ready, set, get healthy! It's meds time. Time for ur [med] now.

5 It's med time, only u can control this. Rmber 2 take ur [med] now. 14 Protect ur health. It's that time again 2 take ur [med] now.

6 Taking ur meds helps control ur disease. Rmber 2 take ur [med] now. 15 It's pill time! Take ur [med] now.

7 Yay, health! Don't frgt 2 take ur [med] now. 16 2 control ur health u need 2 take ur [med] now.

8 Taking ur meds helps 2 keep ur body healthy! Take ur [med] now. 17 Other/Custom

9 U've been doing gr8 w/ ur adherence. It's time 2 take ur [med] now.

0%

10%

20%

30%

40%

50%

60%

70%

80%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Frequency Selected (N=25)


Adherence Rates by Stem

# Stem # Stem

1 Ur health is impt, rmber 2 take ur meds. Take ur [med] now. 10 Adherence is impt. Pls take ur [med] now.

2 Stay healthy! It's time 2 take ur meds, pls take ur [med] now. 11 2 help keep u feeling good, rmber 2 take ur [med] now.

3 No matter what else is going on, it's impt 2 take ur [med] now. 12 Ur meds are important. It's time for ur next dose of ur [med] now.

4 It's med time! Pls take ur [med] now. 13 Ready, set, get healthy! It's meds time. Time for ur [med] now.

5 It's med time, only u can control this. Rmber 2 take ur [med] now. 14 Protect ur health. It's that time again 2 take ur [med] now.

6 Taking ur meds helps control ur disease. Rmber 2 take ur [med] now. 15 It's pill time! Take ur [med] now.

7 Yay, health! Don't frgt 2 take ur [med] now. 16 2 control ur health u need 2 take ur [med] now.

8 Taking ur meds helps 2 keep ur body healthy! Take ur [med] now. 17 Other/Custom

9 U've been doing gr8 w/ ur adherence. It's time 2 take ur [med] now.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Adherence Rate ARV Adherence Rate PSY


iTAB in HIV+ METH Users: iTAB-M


METH is Risk Factor for HIV

In 2008, 850,000 Americans

≥12 y.o. abused METH in

previous year (National Survey

on Drug Use and Health, 2008)

CDC estimates 12% of incident

US HIV cases attributable to

IVDU (HIV/AIDS Surveillance

Report, 2007)

Strong association between

METH use among MSMs and

continued high incidence of

HIV/AIDS in the US (CDC

HIV/AIDS Fact Sheet, 2007)


iTAB-M Focus Groups

AIM:

To identify barriers and strategies for ART adherence specific

to HIV+/MA+ persons and to integrate feedback on the content

of the text-message reminders for iTAB-M

METHOD:

Two focus groups, each with ten HIV+/MA+ individuals, were

conducted

Participants were middle aged (43.6 years, SD=7.7),

predominantly male (90%), Caucasian (60%), and high school

educated (12.3 years; SD=2.8).


iTAB-M Focus Group Data Analysis

Audio recordings transcribed

Independently coded by two investigators using QSR NVivo

software

Codes identified emergent themes related to barriers and

strategies of adherence and feedback on the content of

proposed text messages

Disagreements in coding resolved through consensus

Kappa calculated for final assigned codes

High Interrater reliability: kappa = 98.7


Adherence Barriers in Meth HIV+

Mental Health

Lack of Social Support

Meth-related

Lack of Education

Pill Burden

Accessibility

Apathy

Cognitive Problems

Medicine Side Effects

Stigma

Nodes clustered by Word similarity


Example: Adherence Barriers

My biggest problem was losing track of time,

you know, and so I would have them but I may

take it, you know, 12 hours and then 36 hours

and that kind of deal, but I always adhered. It

was just very sloppy, you know, while I was

using that weekend. So, that was my

biggest issue.

”

“


Strategies for Adherence

Planning

Spirituality

Self Efficacy

Increase Accessibility

Utilize Reminders

Engagement of Health Care System

Efficient Medication Regimen

Health Promotion

Pharmacy Assistance

Self-Esteem

Nodes clustered by Word similarity

Education

Social Support

Token Economy


Strategies for Adherence

I was thinking about taking meds and

things like that, if we have something

called the buddy system. Or just maybe

have one of the nurses giving you a call

everyday saying are you taking your

meds?

”

“


Meth and Adherence

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

Control ITAB

% of Days Reporting Meth Use

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Meth+ days Meth- days

Adherence by Meth Status


Example iTAB-M Intervention Stems

» Celebrate Health

• Stay healthy! It’s time 2 take ur

meds, pls take ur…

» Time and Focus

• It only takes a second! Take ur…

» Social Support

• People care about u. Pls take

ur…

» Control Disease

• It’s impt to take care of urself.

Pls take ur…

» Self-Esteem

• U are special. Pls take ur…

» Meth Focus

• Take ur meds so u can keep

having fun. Time 4 ur…

» Dangers of Non-adherence

• Not taking ur meds could

make u resistant. Take ur…

» Spiritual

• God grant me the serenity to

do this. It’s time 4 ur…

Stems of personal reminder messages reflect different themes:


iTAB-M Intervention Stems

# Reminder Stem

1 Stay healthy! It’s time to take your meds, please take your medications.

2 To help keep you feeling good, remember to take your medications.

3 Ready, set, get healthy! It’s med time. Time for your medications.

4 Live longer! Take your medications.

5 Yay, health! Don’t forget to take your medications.

6 It only takes a second! Take your medications.

7 It's med time! Please take your medications.

8 It’s pill time! Take your medications.

9 No matter what else is going on, it’s important to take your medications.

10 Stop everything and take your meds! Take your medications.

11 People care about you. Please take your medications.

12 Think about the people who love you. Take your medications.

13 We care about u and your health. Please take your medications.

14 [name] needs you. Take your medications.

15 You are not alone. It’s time to take your medications.

16 It’s important to take care of yourself. Please take your medications.

17 Your health is important, remember to take your meds. Take your medications.

18 To control your health you need to take your medications.

19 Adherence is important. Please take your medications.

20 Protect your health. It’s that time again to take your medications.


iTAB-M Intervention Stems

# Reminder Stem

21 You are special. Please take your medications.

22 Stay strong. It’s time for your medications.

23 You’ve been doing great with your adherence. It’s time to take your medications.

24 You can do it! Take your medications.

25 It’s a great accomplishment to be adherent! Take your medications.

26 Take your meds so you can keep having fun. Time for your medications.

27 Ignore Tina and take your medications.

28 It’s not party time; it’s med time! Please take your medications.

29 You can have fun and take your meds. Time for your medications.

30 Stop screwing around and take your medications.

31 Not taking your meds has severe consequences. Take your medications.

32 Not taking your meds could make u resistant. Take your medications.

33 You need your meds to live longer. Time for your medications.

34 You will only get sicker if you don’t take your meds. Time for your medications.

35 Not taking your meds puts others at risk. Please take your medications.

36 God loves you. It’s time for your medications.

37 WWJD? Take his meds! Time for your medications.

38 Trust in the Lord. Take your medications.

39 The Lord believes in you; believe in yourself. Take your medications.

40 God grant me the serenity to do this. It’s time for your medications.


iTAB-M Frequency of Stem Selection

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41


6. It only takes a second! Take your medications.

8. It’s pill time! Take your medications.

9. No matter what else is going on, it’s important

to take your medications.


0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41

Adherence Rate by Stem (N=10)

Self-reported Adherence by Stem

Overall Mean: 64.5%


Frequency Chosen by Adherence

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41

Adherence Rate



iTAB in HIV- for PrEP: CCTG 595


Controlled, un-blinded, two-armed, randomized (1:1)

clinical trial in the setting of PrEP implementation at three

HIV testing/ HIV provider sites in Southern California

Randomized either to

PrEP + SoC or

PrEP + SoC + iTAB

Duration: endpoint analysis at 48 weeks

Sample size: 400 subjects, 200 per arm

Stratification by clinic site

Study Design


CCTG 595 Schema


CCTG 595 Hypotheses

Objective: To compare adherence to fixed dose TDF/FTC,

between subjects randomized to receive SoC plus text

message reminders versus SoC, when used for pre-

exposure prophylaxis among MSM at high risk for HIV

acquisition

Hypothesis: MSM and transgender M to F having sex with

men with high risk of HIV acquisition randomized to the

iTAB intervention will have higher self-reported adherence

to TDF/FTC for PrEP over 48 weeks (‘adherent’ defined with

a composite endpoint of continued retention on PrEP and >

90% adherence to TDF/FTC at 48 weeks) compared to

MSM that have comprehensive SoC alone


CCTG 595 Focus Group 1

Mixed Group of HIV+ and HIV- individuals

About half of the participants knew of PrEP

Liked the idea of medication reminders via text

If to ask about unprotected sex, ask very directly


CCTG 595 Focus Group 2

HIV- only

Liked idea of medication reminders via text

Specific Feedback on System:

» System needs to be varied; prefer no repeat messages

» Want daily messages for 48 weeks

» Want short messages, no names or med description.

» Want fun, witty, playful messages (e.g., snapple facts)

» Interested in selecting messages by domain related to interests;

not specifc messages (e.g., want to be surprised)

» Prefer not to have medication name or any mention of med or drug

» Provided good examples: “Pill O’Clock” “Med Thirty” “Y.O.L.O”

Similar for other groups, SES?


Conclusions & Future Directions

iTAB :

1.Higher ARV adherence in HIV+/BD+ as compared to

observational study

2.Significantly better dose timing improves therapeutic

coverage iin HIV+/BD+

3.Different stems/reminders may be needed by group (Meth

using)

4.Interventions for PrEP may need to be highly different from

those for HIV


Future Directions

1. Continue enrollment of iTAB-M (Refer Patients: 619-543-

5000)

2. Refine and implement system for CCTG 595

3. Evaluate iTAB over longer periods of time

4. Begin development of app for targeted group via SBIR

collaboration


Acknowledgments

Participants

Funding Support

» California HIV/AIDS Research Program ID-

09-047, EI-11-SD-005

» NIDA R34 DA31058

» NIMH/CSPAR P30 MH062512

Co-investigators/Consultants

» J. Hampton Atkinson, M.D.

» Colin Depp, Ph.D.

» Igor Grant, M.D.

» Richard Haubrich, M.D.

» Scott Letendre, M.D.

» Sheldon Morris, M.D., M.P.H.

» Tom Patterson, Ph.D.

» Steven Safren, Ph.D.

Students

» Kaitlin Blackstone

» Shereen Georges

» Jessica Montoya

» Carolina Posada

Fellows

» Pariya Fazeli, Ph.D.

» Maria Marquine, Ph.D.

Staff

» Jayraan Badiee

» Candy Carson

» Eric Ellorin

» Roberto Gallardo

» Ben Gouaux

» Jenn Marquie-Beck

» Amelia Poquette

» Alexandra Rooney

» Crossby Vargas

» Mel Willard

Cal-IT2 Technical Experts

» Kevin Patrick, M.D., M.S.

» Allison Flick

» Fred Raab

» Mark Sullivan


Documents

Update on Individualized Texting for Adherence Building (iTAB): Lessons for Implementation