1. Cell phones for HIV Care and Health Promotion: What Works Richard Lester, MD, FRCPC BCCDC University of British Columbia BCCDC and University of British ColumbiaWelTel.org Saskatoon HIV AIDS Research Endeavour (SHARE) May 15, 2012

2. Disclosures – support received Non-corporate PEPFAR CDC/CDC Foundation WHO BCCDC Foundation IDRC/GHRI AMMI/CIHR/BMS Gates Foundation ICID (UManitoba) NIH (NIMH) Corporate Bristol-Myers-Squibb

3. mHealth mHealth: What is it?  Wikipedia: a term used for the practice of medical and public health, supported by mobile devices.  NIH: the delivery of healthcare services via mobile communication devices  Emerged as a sub-segment of eHealth: computers, mobile phones, communications satellite, patient monitors – Using information and communication technology (ICT) for health services and information, such as computers, mobile phones, communications satellite, patient monitors, etc, for health services and information.

4. Is it all

5. CREDIT: http://www.armybase.us/2009/04/air-force-yields-in-f-22-fighter-dispute/

6. mHealth applications Emergency response systems (e.g., road traffic accidents, emergency obstetric care) Human resources coordination, management, and supervision Mobile synchronous (voice) and asynchronous (SMS) telemedicine diagnostic and decision support to remote clinicians Clinician-focused, evidence-based formulary, database and decision support information available at the point-of-care Pharmaceutical Supply Chain Integrity & Patient Safety Systems (e.g. Sproxil and mPedigree) Clinical care and remote patient monitoring Health extension services Health services monitoring and reporting Health-related mLearning for the general public Training and continuing professional development for health care workers Health promotion and community mobilization Support of long-term conditions, for example in diabetes self-management Wikipedia, accessed Jan 30, 2012

7. HIV-Not Hype? Problem Problem: People living with HIV Response Response: People on ARTPeople with mobile phones

8. Kenya Population= 39,002,772 7.1% 2007 adult HIV prevalence 1 physician/2 nurses per 10,000 population ~16 million mobile phone subscribers Kenya: Dual Epidemics Lester et al. AIDS Vol 20, 17 Nov, 2006 2005

9. Can cellphones improve HIV care?

10. WelTel Kenya1: RCT Screening (581+) Randomized (538) Pumwani (251) SMS (120) Follow-up control (131) Follow-up Coptic (209) SMS (117) Follow-up control (92) Follow-up Kajiado (78) SMS (36) Follow-up control (42) Follow-up Inclusion Adults (> 18 years) starting ART Adequate phone access (owned/shared) Informed consent Randomization Baseline survey 6 month 12 month Powered to show 10% improvement in adherence Exclusion (44) Inadequate phone access Refused/Unable SMS n=273 Control n=265

11. WelTel Kenya1: 2-way weekly (SMS) interactive check-ins. n=11,983 SMS logs (6.1% ‘SHIDA’) (2.0% ‘SHIDA’)

12. WelTel Kenya1 Reason for SHIDA responses Problem responses*Unique problem responses * Total377 (100)140 (100) Health issues 272 (72) 121 (86) Non-health issues 40 (11) 33 (24) Missing/unreachable 67 (18) 50 (36) Reason participant did not respond Non-responses n=3730 n (%) ƚ Unique participant non-responses n=260 n (%) ƚ Cell phone problems822 (22) 205 (79) Participant factors463 (12) 172 (66)

13. Outcome (ITT) SMS group no. (%) Control group no. (%) RR (95%CI) P value Self-reported adherence (> 95%)168 (62)132 (50) 0.81 (0.69 - 0.94) 0.006 Viral suppression (<400 copies/ml)156 (57)128 (48) 0.85 (0.72 - 0.99) 0.040 Ancillary analysis Complete case Adherence (n=358) Viral suppression (n=400) 168 (91) 156(75) 132 (91) 128 (66) 1.00 (0.94 – 1.07) 0.88 (0.77 - 1.00) 0.94 0.047 WelTel Kenya1: Outcomes

14. WelTel Kenya1: Subgroup analysis (VL)

15. Summary SMS patients 24% more likely to be adherent to ART (NNT=9) SMS patients 19% more likely to have suppressed VL (NNT=11) 98% said would like program to continue 97% said would recommend it to a friend Lester & Karanja Lancet Infectious Diseases Vol 8 December 2008

16. Western Kenya RCT: One-way SMS ‘reminders’ Pop-Eleches et al. AIDS, 2011 Adherence by MEMS caps: daily vs. weekly & long vs. short reminders (VL not available.)

17. Two Randomized Controlled Trials (Kenya) March 27, 2011Nov 27, 2010

18. Summary Short, weekly reminders improved adherence – Weekly reminders 53% achieved 90% adherence – Control 40% achieved 90% adherence (p=.03) Daily reminders no effect LEVEL 1b Evidence that Weekly SMS can improve ART adherence. Centre for Evidence-Based Medicine, Oxford

19. 243 references ID’d to Nov 2011:

20. What doesn’t work?

21. Nairobi Kenya RCT: ART counselling vs. reminders Chung et al. PLoS Med, March 2011 reminder alarm device A medication reminder alarm device had no effect on adherence or viral suppression

22. Emerging ART adherence innovations: ABSTRACT: Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6.Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 ± 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue. Boston Medical Centre

23. Other Innovations: TBD Real-Time Electronic Adherence Monitoring is Feasible, Comparable to Unannounced Pill Counts, and Acceptable. AIDS Behav. 2011 Mar 30. Haberer JE, Robbins GK, Ybarra M, Monk A, Ragland K, Weiser SD, Johnson MO, Bangsberg DR. Source Harvard Institute for Global Health, 104 Mt Auburn St, 3rd floor, Cambridge, MA, 02138, USA, jhaberer@partners.org. Abstract Second generation electronic medication adherence monitors provide real-time data on pill bottle opening behavior. Feasibility, validity, and acceptability, however, have not been established. Med-eMonitor is a multi-compartment adherence device with reminder and education capacity that transmits data through a telephone connection. Monthly adherence levels were measured for 52 participants over approximately 3 months using the Med- eMonitor (unadjusted and adjusted for participant confirmed dosing) and unannounced pill counts. HIV RNA was assessed before and after the 3-month period. Acceptability of Med- eMonitor was determined. Over 92% of Med-eMonitor data was transmitted daily. Unannounced pill counts significantly correlated with adjusted Med-eMonitor adherence (r = 0.29, P = 0.04). HIV RNA significantly correlated with unannounced pill counts (r = -0.34, P = 0.02), and trended toward a significant correlation with unadjusted Med-eMonitor adherence (r = -0.26; P = 0.07). Most, but not all, participants liked using the Med-eMonitor. Med-eMonitor allows for real-time adherence monitoring and potentially intervention, which may be critical for prolonging treatment success.

24. Other cell phone studies AIDS Patient Care STDS.AIDS Patient Care STDS. 2011 Mar;25(3):153-61. Epub 2011 Feb 16. Randomized controlled trial of a personalized cellular phone reminder system to enhance adherence to antiretroviral therapy. N=19 adults Hardy HHardy H, Kumar V, Doros G, Farmer E, Drainoni ML, Rybin D, Myung D, Jackson J, Backman E, Stanic A, Skolnik PRKumar VDoros GFarmer EDrainoni MLRybin DMyung DJackson JBackman EStanic ASkolnik PR Trials.Trials. 2011 Jun 9;12:145. The challenges and opportunities of conducting a clinical trial in a low resource setting: the case of the Cameroon mobile phone SMS (CAMPS) trial, an investigator initiated trial. N=198 adults Mbuagbaw LMbuagbaw L, Thabane L, Ongolo-Zogo P, Lang T.Thabane LOngolo-Zogo PLang T AIDS Patient Care STDS.AIDS Patient Care STDS. 2011 May;25(5):303-10. Epub 2011 Apr 2. Brief behavioral self-regulation counseling for HIV treatment adherence delivered by cell phone: an initial test of concept trial. N=40 adults Kalichman SCKalichman SC, Kalichman MO, Cherry C, Swetzes C, Amaral CM, White D, Jones M, Grebler T, Eaton L.Kalichman MOCherry CSwetzes CAmaral CMWhite DJones MGrebler TEaton L Lancet.Lancet. 2011 Aug 27;378(9793):795-803. Epub 2011 Aug 3. The effect of mobile phone text-message reminders on Kenyan health workers' adherence to malaria treatment guidelines: a cluster randomised trial. N=2269 children Zurovac DZurovac D, Sudoi RK, Akhwale WS, Ndiritu M, Hamer DH, Rowe AK, Snow RW.Sudoi RKAkhwale WSNdiritu MHamer DHRowe AKSnow RW

25. How do cell phone communications improve ART adherence? Adherence to antiretroviral therapy: supervision or support? Adherence to antiretroviral therapy: supervision or support? – Lancet Infectious Diseases, February 2012 – http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70354-1/fulltext http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70354-1/fulltext Adherence and Retention – social capital? Binagwaho A, Ratnayake N (2009). PLoS Med 6(1): e18.

26. mHealth for HIV/AIDS control: Where is it going? What is the potential impact? Improved adherence and viral suppression (retention?) 1.Improves health 2.Improves society 3.Improves economy 4.Reduces costs (drug resistance) 5.Controls pandemic (treatment as prevention) Challenges: Can it be improved? Is it cost-effective? Can it be scaled up?

27. M-powered The convergence of mobile telephony and health care is under way Wireless health care...Mr Gates, however, warned the participants not to celebrate too soon. Just because an m- health pilot scheme appears to work in some remote locale, he insisted, don’t “fool yourself” into thinking it really works unless it can be replicated at scale. Rafael Anta of the Inter- American Development Bank was even more cautious: “We know little about impact and nothing about business models.” Happily, evidence of m-health’s usefulness is at last starting to trickle in. A study this week in the Lancet, a medical journal, shows that something as simple as sending text messages to remind Kenyan patients to take their HIV drugs properly improved adherence to the therapy by 12%.... “Middle-income countries are where most innovation in health care is going to come from.” Nov 11th 2010 | WASHINGTON, DC | from the print edition

28. mHealth Summit 2012 (Bella Hwang) Scale-up 1.Kenya – approx. 500, 000 ART patients 2.PEPFAR (global) – approx. 2.5 million ART patients Costs Activity Based Costing – SMS Intervention: $11.75 USD/year per patient – Kenya $10.21 USD/year per patient - PEPFAR Cost Savings Models used: Freedberg et al. J Acquir Immune Defic Syndr 2006; 43(Suppl 1):S113-118. Bishai D et al. AIDS 2007; 21(10):1333- 1340. Grant AD et al. Am J Trop Med Hyg 2001 65: 810-21.

29. mHealth Summit 2012 (Bella Hwang) PEPFAR (n=2.5 million)

30. UNAIDS: 2010 Global Report

32. New Projects www.weltel.org

33. Harnessing mobile phone usage for HIV and horizontal health systems improvement: Prevention of mother-to-child transmission (PMTCT) Pumwani Maternity Hospital, Nairobi PRINCIPAL RESEARCHER: Joshua Kimani, University of Nairobi, Kenya PRINCIPAL DECISION-MAKER Peter Cherutich, Ministry of Health, Kenya Africa Health Systems Initiative Support to African Research Partnerships (AHSI-RES)

34. This study, funded by the NIH, will be conducted with AMREF and will involve over 700 participants at the Kibera Community Health Centre in Nairobi, Kenya. WelTel Retain Promoting engagement in pre-ART HIV care through SMS This study will determine if the WelTel intervention improves patient retention in the first stage of HIV care and at 12-months. We will also evaluate the cost- effectiveness of the intervention.

35. What about here? 65,000 people living with HIV ~72% of ALL Canadians (24 million people) have a cell phone!

36. WelTel: LTBI Latent Tuberculosis Infection Only 50 – 60% complete therapy for LTBI (BCCDC) Pilot – 16 patients –median age of participants was 47 (range 21-82) –(56%) were female. (n=14) –79% of participants would like the program to continue and 86% would recommend it to a friend. –Report side effects quickly (93%) –helped them feel hopeful about their care (100%). BC Lung Association: Randomized control trial (RCT)

37. WelTel BC1 (HIV) Oak Tree Clinic – HIV support for women and families Informative study Clinic client survey Pilot: 5x5 SMS <24y Youth >50y Mature >3h away Remote Immigrants ESL: Poor adherence Non- suppressed Support: Bristol-Myers Squibb (BMS) through BCCDC Foundation 5x5 SMS pilot

38. Barriers to adherence Forgetting Drug use Co-morbid depression Side effects Lack of social support http://womenonthefence.com/wp-content/uploads/2011/06/depression.jpg http://z.about.com/d/hepatitis/1/0/k/0/-/-/InjectingDrugs.jpg http://frank.itlab.us/forgetting/think.gif http://forladiesbyladies.com/wp-content/uploads/2010/02/3_vomiting.jpg

39. Pre-Study Questionnaire Clinic attendants were asked to fill out a brief questionnaire re: – Cell phone possession and use. – Thoughts about mHealth interventions. – Age – Language – Gender langleytoday.ca

40. Demographics Languages used At home # (%) To text # (%) English152 (82.6%)170 (94.4%) French6 (3.3%)3 (1.7%) Punjabi7 (3.8%)1 (0.6%) African10(5.4%)2 (1.1%) 1 st Nations1 (0.5%)0 (0%) European5 (2.7%)2 (1.1%) Asian3 (1.6%)2 (1.1%) DemographicsNumber(%) (n=180) Age: median(range)39 (11-63) Gender Female Male Transgender 136 (78.2%) 35 (26.1%) 3 (1.7%) A majority of patients used English at home, but an even greater number used English when texting.

41. Cell phone stats… Cell Phone StatisticsNumber (%) Own a cell phone No Yes-basic Yes-smart phone 33 (19.0%) 80 (46.0%) 61 (35.0%) Share a cell phone Yes-household Yes-other 13 (7.5%) 6 (3.4%) Have texting plan No Yes-pay/text or limited Yes-unlimited 21 (14.5%) 33 (22.8%) 91 (62.7%) Have internet on phone No Yes 95 (60.9%) 61 (39.1%) Frequency of texting Never Rarely (once/month) Occasionally (once/week) Frequently (few/week) Very frequently (daily) 37 (22.3%) 11 (6.6%) 19 (11.4%) 41 (24.7%) 58 (34.9%) 180 patients polled 81% owned a cell phone 88% used text messaging 43% of above access the internet from their phone 71% text message at least weekly 83% believed the intervention could assist in clinical care/follow up

42. Risks and benefits… Perceived Benefits/RisksNumber (%) “Could this intervention benefit you?” No Yes Don’t know 22 (12.6%) 109 (62.6%) 43 (24.7%) “What are the benefits?” Easy access to care Reminders Ability to contact Multiple Reasons Would rather text 14 (20.6%) 18 (26.5%) 29 (42.6%) 4 (5.9%) 3 (4.4%) “What are the risks / concerns?” None Confidentiality Other 84 (62.7%) 36 (26.9%) 14 (10.4%) 2/3 felt the intervention could benefit them Major concern: confidentiality

43. The Intervention Platform sends SMS “How are you?” Positive response (ex: “I’m good”) Negative response (ex: “I have a question”) No response in 48 hrs SMS: “Great, text you again next week” Phone call from RN SMS: “I haven’t heard from you, everything okay? Positive response Negative or no response

44. Gaps in care: Avoidance “ I think I was depressed, or in a rut or something. I didn ’ t feel like going anywhere or doing anything … The doctor started getting a hold of me and they asked me to start coming back in again. And then [outreach worker] makes it easy. ” – Non-suppressed “ I don ’ t know, maybe I just got tired of medicine … I didn ’ t want to tell anybody, I just I didn ’ t want to share to anybody. Myself I don ’ t even know why. I know it was not a good thing to do. ” – ESL “ I ’ ve avoided the clinic at times, but usually because there was something wrong and I didn ’ t want to deal with it … I ’ d come in and see [doctor], I just would avoid the gynecologist because I didn ’ t want to go and find out if I had cancer or not. ” - Distance

45. Interest in Texting It wouldn’t bug me, it would make me think that somebody cares, actually.” – Non suppressed I feel like with text messaging you can just ask whatever you want and it’s not going to be something that’s going to be like embarrassing or, like, I just feel more comfortable texting ” - Youth “Just a good reminder as well. You know, little things, and you know, keeping me on track, keeping me in touch, right, that’s always a good thing.” - Mature Texting would be great… I like to stay in contact with Oaktree. It’s important to me because I haven’t been well. So to be able to have continuous contact with them, and I haven’t… because of lack of phone and stable living environment.” – Non suppressed I could tell you right now that I have several clients that I think that would really benefit who right now we have no way of communicating with, right, and who are less likely to come to the clinic. – Healthcare worker “I’m really technology literate, and it would just make my life a lot easier to be able to text my doctor” - Youth

46. Concerns about Texting “If you’re sending a text, I should know who’s texting and their questions. It shouldn’t always be on HIV.” - ESL If there’s a serious problem I want to talk to somebody, I don’t want to text them, especially if I’m sick”- Mature “Privacy is a must” - ESL I think one thing is to get hold of them, and the other thing is actually to provide care. And sometimes even if you actually get hold of them, that doesn’t necessarily mean that you actually provide care. – Healthcare worker “A text message usually prompts other work: so, consulting other team members, or pulling lab results, or doing other things, so that volume could increase” – Healthcare worker The only problem I would have probably in the future would be with the arthritis… right now my wrists and my thumbs are pretty sore” – Mature

47. Nursing Practice Hi! This is Karen, we changed the ultrasound appt to thurs at 10am. There r a couple of instructions. Is there a number I can call u on? Thurs at 10am at [location]. U have to eat a fat free supper on Wed and then fast from midnight on. When is the appt? Dr. M wants to ask how your breathing is these days. Have u been able to take the septra? How are you? I’m ok I missed my ultrasound yesterday can u rebook please?

48. Nursing Practice Hi! This is Karen, I’m sorry to hear that [name]. Let us know if there is anything we can do to support you.” It b gd to find a frief counselor.. My x mother in law passed away in April too along w/ 2 friends up north.. April has been very heart breaking Patient put in contact with Oak Tree counselor who referred patient to grief counselors closer to her, as well as opportunities for aboriginal healing ceremonies. How are you? A really gd friend of ours was murdered last thurs.. she was only 23

49. Examples of Texting… WTBC1-14 (Mature) Subject: “So im on my way getting my six month at home group I feel awesome awesome the best yet :-*” Patient letting us know how she is doing. This patient was given a phone and taught to text because of WelTel BC1. WTBC1-04 (Youth) WelTel: “How are you?” Subject: “Good” A typical response from youth in WelTel BC1 so far.

50. NIH: EPIC NIH: EPIC Enhance PrEP in Communities San Francisco Department of Public Health Albert Liu, Jonathan Fuchs et al. Interactive SMS + Next step counselling to improve adherence Potential deployment sites: US (San Francisco, Boston) Peru (Lima and Iquitos) Brazil (Rio and Sao Paolo) others

51. Summary of RCT Evidence on mHealth Interventions to improve ART outcomes Adherence monitoring by SMS? - ? – not yet known if effective for adherence promotion – Challenging to implement, cost, compliance, stigma? Targeted adherence counselling? - Y – improves adherence and viral suppression (1yr) Digital alarm reminders? - N – No improvement on adherence or VL (1yr) One way cell phone SMS reminders? – N/Y – no improvement in adherence (by MEMS), for daily reminders – effective with short weekly messages. (1yr) Two-way cell phone SMS çheck-ins’/access to HCW? -Y – Improves adherence and viral suppression (1yr) Level of Evidence: Level of Evidence: Grade A (weekly SMS) Support (access to care) > Reminders? Adherence to antiretroviral therapy: supervision or support? Lancet ID, Feb 2012 http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70354-1/fulltext

52. My take home messages Keep it simple – Every extra step (complexity) loses someone Keep it low cost – Resource limited settings, vulnerable groups Conduct controlled studies – What really works, and what doesn’t Seize the opportunity – mHealth is a gift

53. The future is now

54. “All I’m saying is now is the time to develop the technology to deflect an asteroid.” Thanks!

55. Ref: Audio & Visuals Lancet podcast – http://download.thelancet.com/flatcontentassets/audio/lancet/2010/9755_27novembe r.mp3 http://download.thelancet.com/flatcontentassets/audio/lancet/2010/9755_27novembe r.mp3 Scientific American podcast (1min) – http://www.scientificamerican.com/podcast/episode.cfm?id=text-message-outreach- improves-hiv-10-11-10 http://www.scientificamerican.com/podcast/episode.cfm?id=text-message-outreach- improves-hiv-10-11-10 CBC News The National (3min) – http://www.cbc.ca/video/#/Shows/1221254309/ID=1380546967 http://www.cbc.ca/video/#/Shows/1221254309/ID=1380546967 The Economist: – http://www.economist.com/node/17465455 http://www.economist.com/node/17465455