Richard Garfein, PhD, MPH Professor Herbert Wertheim School of Public Health and Human Longevity Science Adjunct Professor Division of Infectious Disease and Global Public Health Department of Medicine University of California, San Diego

1. HIV & Global Health Rounds
The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease and global public health clinicians,
physicians, and researchers. The goal of these presentations is to
provide the most current research, clinical practices, and trends in HIV,
HBV, HCV, TB, and other infectious diseases of global significance.
The slides from the HIV & Global Health Rounds presentation that you
are about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.

2. Video DOT for Monitoring Treatment
Adherence for TB, LTBI and Beyond
Richard S. Garfein, PhD, MPH
Herbert Wertheim School of Public Health
UC San Diego
HIGH Rounds
January 22, 2021
2

3. Disclosures
• Dr. Garfein is a cofounder of SureAdhere Mobile
Technology, Inc., a VDOT service provider. No funding,
software, or other resources were provided by
SureAdhere for the studies presented.
• To mitigate potential conflicts of interest, all interpretation
and reporting of the study findings were approved by
coauthors who are unaffiliated with SureAdhere. The
terms of this arrangement have been reviewed and
approved by USCD in accordance with its conflict of
interest policies.
3

4. Medication Non-Adherence
• Annual costs of medication non-adherence range from
$100 to $290 billion in the USA1
• Leads to poor health outcomes
• Leads to antimicrobial resistance
1New England Healthcare Institute. Thinking outside the pillbox: a system-wide approach to improving patient medication
adherence for chronic disease. 2009
http://www.nehi.net/publications/44/thinking_outside_the_pillbox_a_systemwide_approach_to_improving_patient_medication_adhe
rence_for_chronic_disease (accessed 24 Jun 2016).

5. First-Line TB Treatment
Initial phase (8 weeks):
• 4 drugs daily (~500 pills)
Continuation phase (18 weeks):
• 2 drugs daily (~500 pills)
~1000 pills over 6 months
CDC, http://www.cdc.gov/tb/topic/treatment/tbdisease.htm
The WHO estimates that 30-50% of TB
patients fail to take their medication doses
as prescribed.

6. 6
Does adherence really matter in TB?
Source: TB ReFLECT Consortium, unpublished data3
TB patients taking RIPE with <90%
adherence had 5.6 times increased risk of
TB recurrence in a meta-analysis of the
OFLOTUB, REMox, and Rifaquin trials.
Study of 534 smear-positive patients in India
found a strong relationship between adherence
and post-treatment TB recurrence.
Severity of non-
adherence
TB recurrence
rate, 18 months
after completing
treatment
“Regular”
adherence
9%
“Irregular”
adherence
15%
“Very irregular”
adherence
25%
Source: Thomas et al. Int J TB Lung Dis 2005; 9(5): 556-614
Slide courtesy of Bruce Thomas, The Arcady Group

7. 7
Does adherence really matter in TB?
“Modeling study shows the risk of generating
MDR-TB de novo is highest between 40%
and 80% adherence.”
“[P]robably the cheapest and most effective
way to ensure a positive treatment outcome
while minimizing the risk for the emergence
of MDR-TB is to maintain proper patient
compliance with the treatment.”
Cadosch et al. Plos Comp Bio 2016;12:e10047498

8. Monitoring TB Medication Adherence
• Purpose:
• Document that all doses were taken
• Promote treatment completion
• Detect drug adverse effects
• Goals:
• Reduce TB morbidity and mortality
• Prevent TB transmission
• Prevent acquired drug resistance

9. Directly Observed Therapy (DOT)
• Patient observed swallowing each dose
• Recommended by CDC & WHO
• Rationale:
• Improves adherence
• Reduces risk of acquired drug resistance,
treatment failure, and relapse
• Establishes rapport with patients
• Allows intermittent dosing
Community-Based DOT
Clinic-Based DOT

10. Cost
Personnel
Travel
Privacy
and
Stigma
Patient
Autonomy
Barriers
to DOT
COVID-19

11. Impact of COVID-19 on TB Control
Stop TB Partnership Report focused on three
high burden settings: India, Kenya and Ukraine
• TB case notifications in January–May 2020
decreased drastically compared with the same
period in 2019 (36%) and 2015 (52%).
• TB treatment completion rates were reduced
from 60% in 2019 to 51% for the same period
in 2020.
• Screening for TB drug resistance also
declined significantly during 2020.
Stop TB Partnership.
http://www.stoptb.org/assets/documents/news/Modeling%20Report_1%20May%202020_FINAL.pdf.
Figure 1. Dynamics of TB incidence and mortality following a COVID-19 lockdown
Figure 2. Accelerating the recovery from lockdown-induced setbacks to TB control

12. Impact of COVID-19 on TB
• Disrupted transportation and restricting health facilities to
emergency services impairs access to TB diagnosis and
treatment services.
• TB treatment disruptions were reported by nearly 80% of
Global Fund-supported TB programs; 17% reported high
to very high disruptions.
• Modeling studies predict an additional 6.3 million cases of
TB and 1.4 million deaths over the next 5 years due to
COVID-19-related disruptions.
• TB control set back 5-8 years, receding even further away
from the 2030 target of TB elimination.
• Pandemic makes DOT even more challenging!

13. Can Digital Adherence Technology Help?
• 99DOTS
• WisePill
• SMS
• Ingestible
sensors
• A.I. observation
• Reminder apps
• Video observed
therapy

14. Other Digital Adherence Technologies
• Pill-in-hand
• Electronic pill dispensers (MEMS Caps, pill boxes)
• 99DOTS
• SMS
• Pill-in-mouth
• Metabolic tests (urine, blood, hair)
• Ingestible sensors (Proteus)
• Video DOT

15. Video Directly Observed Therapy (VDOT)
Synchronous VDOT
• Videoconferencing
• “Real-time” or “Live”
Asynchronous VDOT
• Recorded videos
• “Store-and-forward”

16. Synchronous VDOT Process
Scheduling
Connecting
Observing
Documenting
16

17. Synchronous VDOT
Evidence
• High adherence/completion1-3,5-7
• High patient & provider
satisfaction1,3-6
• Resource saving1-5,7
Limitations
• Restricted to business hours
• Scheduling takes staff time
• Dosing times not always
acceptable to patients
• Requires reliable connectivity
• Not all video-conferencing apps
meet security standards for PHI
(i.e., HIPAA or GDPR)
1DeMaio, et al., Clin Infect Dis, 2001; 2Krueger, et al., Int J Tuberc Lung Dis, 2010; 3Gassanov, et al., Can J Public Health, 2013; 4Bethel, et al., ATS
Conf., 2006; ; 5Mirsaeidi, et al., Eur Resp J, 2015; 6Wade, et al., PLoS One, 2012; 7Chuck, et al., Int J Tuberc Lung Dis, 2016
17

18. Asynchronous VDOT Process
Review
Observe Document
Store
Secure cloud or local server
Record
Date/ Time
stamp
Encrypt Upload
18

19. Patient Dashboard helps providers
visualize how each dose was taken,
and immediately identify missed
doses.
Provider Dashboard shows adherence at the
patient and program level. Missed and taken
doses are color-coded for easy identification

20. First Asynchronous VDOT Study
• 13 patients, 3 healthcare providers
• Treatment supporters used smartphone to video patients
• Patients received educational SMS and video messages
• Followed for 30 days
Patients, providers and supporters agreed that VDOT was a
viable option; 8 (62%) patients preferred VDOT over DOT
Patients and providers reported being empowered by the
ability to communicate with each other through technology
(Am J Prev Med 2010;39(1):78 – 80)

21. First Asynchronous VDOT Study in U.S.
• Objective:
• To assess the feasibility, acceptability and potential efficacy
of VDOT for monitoring TB treatment
• Setting:
• TB control programs in San Diego County and Tijuana
• Implemented by TB program staff
• Design:
• Phase I – Focus groups (patients, providers, health officers)
• Phase II – Single-arm pilot trial
• Eligibility: Age>18; pansensitive pulmonary TB; DOT-experienced
• Patients interviewed pre & post VDOT use
(Funding: NIH R21-AI088326; PI: R. Garfein)

22. VDOT Pilot Trial - Demographics
San Diego
(n=43)
Tijuana
(n=9)
Spent time in both cities n (%) 6 (14.0) 0 (0)
Age: mean(range) 38.9 (18-86) 28.1 (18-65)
Hispanic or Latino: n (%) 18 (41.9) 9 (100)
Race: n (%)
Asian
African American/Black
Pacific Islander/Native Hawaiian
Caucasian/White
Other/Mixed Race
13 (30.2)
3 (6.9)
2 (4.7)
9 (21.0)
16 (37.2)
0 (0)
0 (0)
0 (0)
3 (33.4)
6 (66.6)
Female: n (%) 20 (46.5) 4 (45.5)
Had to switch back to in-person DOT: n (%) *6 (13.9) 1 (11.1)
Telephones stolen/replaced: n/n 1/2 2/1
*3 patients with drug resistant TB returned to in-person DOT per protocol.

23. VDOT Pilot Trial - Results
San Diego
(n=43)
n (%)
Tijuana
(n=9)
n (%)
Adherence (doses observed/expected) 93% 96%
Rarely/never had problems making videos 35 (85) 8 (89)
Prefer VDOT over DOT if had to repeat Tx 38 (93) 8 (89)
Would recommend VDOT to other TB patients 41 (100) 9 (100)
Found VDOT more confidential than DOT 35 (85) 7 (78)

24. Three City VDOT Trial
• Objective:
• To see if VDOT results vary by location
• Setting:
• TB control programs in 3 high burden metropolitan areas
(San Diego, San Francisco, and New York City)
• Implemented by TB program staff
• Design:
• Single-arm pilot trial
• Eligibility: Age >18, prescribed Tx for DS-TB or DR-TB
• Followed >2 months using VDOT
• Patients interviewed pre- & post-VDOT
(Funding: Verizon Foundation; PI: R. Garfein)

25. Adherence and Participant Experience using
VDOT by City
Variable
San Diego
(n=52)
n (%)
San Francisco
(n=49)
n (%)
New York City
(n=48)
n (%)
P
FEDO
†
: Median [IQR] 88 [33-100] 93 [39-99] 85 [44-100] 0.099
Duration of VDOT use (months): Median [IQR] 5.4 [0.3-14] 5.6 [1-18.1] 5.0 [0.3-14] 0.685
Ever fail to record a video because you were worried
someone might see you taking your medicine? (No) 39 (90.7) 42 (89.4) 28 (90.3) 1.000
Confidentiality of VDOT versus DOT?
More confidential
Less confidential
No difference
25 (58.1)
2 (4.7)
16 (37.2)
33 (70.2)
1 (2.1)
12 (25.5)
17 (54.8)
2 (6.5)
12 (38.7)
0.519
Overall, how did you find the VDOT process?
Very easy
Somewhat easy
Somewhat difficult
32 (74.4)
11 (25.6)
0 (0)
38 (80.9)
5 (10.6)
4 (8.5)
25 (80.6)
6 (19.4)
0 (0)
0.074
Would choose VDOT over DOT if Tx re-done (Yes) 41 (95.3) 45 (95.7) 26 (83.9) 0.172
Would recommend VDOT to other TB patients (Yes) 40 (93.0) 45 (95.8) 29 (93.5) 0.573
VDOT, video directly observed therapy; DOT, directly observed therapy; FEDO, fraction of expected doses observed.
†FEDO = number of complete doses observed via VDOT divided by the number of doses expected.
Int J Tuberc Lung Dis 2020;24(5):520-525

26. Urban Versus Rural VDOT Trial
• Objective:
• To assess the feasibility, acceptability and potential efficacy of
VDOT for monitoring TB treatment in 5 CA counties
• Setting:
• 3 urban (San Diego, San Francisco, Santa Clara) and 2 rural
(San Juaquin, Imperial) TB control programs in California
• Design:
• Quasi-experimental trial
• VDOT (prospective) n=174
• DOT (historical) n=159
• Eligibility: Age >18, prescribed Tx for DS-TB or DR-TB
• Followed >6 months
• VDOT patients interviewed pre- & post-treatment
(Funding: California Healthcare Foundation; PI: R. Garfein) Emerging Infectious Diseases •
www.cdc.gov/eid • Vol. 24, No. 10, Oct. 2018

27. TB TreatmentAdherence by VDOT and DOT
California – 2015-2016
Urban Rural
San Diego
(n = 100)
San
Francisco
(n = 99)
Santa Clara
(n = 49)
Imperial
(n = 11)
San Joaquin
(n = 15) P
Months on VDOT: median (IQR) 5.2 (3.2-6.3) 5.4 (3.5-7.3) 5.5 (4.1-8.1) 4.0 (2.1-5.6) 6.1 (4.4-7.7) 0.08
FEDO: median (IQR)
88.7%
(77%-94%)
95.5%
(87%-98%)
95.2%
(89%-98%)
84.5%
(78%-94%)
96.1%
(93%-98%)
<0.001*
*Rural vs. urban difference not statistically significant.
FEDO = number of doses observed
divided by number of doses
expected
Adherence = number of doses
observed via DOT divided by
number of prescribed doses
Emerging Infectious Diseases 2018;24:1806-1815

28. Factors Associated with FEDO*
California – 2015-2016
Beta
coefficient
Standard
error
P-value
Months on VDOT (per month) 0.008 0.003 0.01
Country of birth: (ref: other)
Mexico -0.095 0.022 <0.001
United States -0.048 0.022 0.03
Felt VDOT was: (ref: very easy)
Somewhat easy -0.003 0.024 0.90
Somewhat/very difficult -0.130 0.042 0.002
Took medications while away from home (ref: never/rarely)
Less than half /half of the time -0.004 0.020 0.83
Most of the time/always -0.049 0.021 0.02
Had problems using the VDOT application (ref: never)
Rarely -0.001 0.018 0.97
Less than half of the time -0.040 0.029 0.16
More than half of the time -0.220 0.041 <0.001
FEDO, fraction of expected doses observed; VDOT, video directly observed therapy.
*FEDO = number of complete doses observed via VDOT divided by the number of doses expected.

29. VDOT Trial – Baltimore, MD
Methods:
• Pragmatic, prospective pilot study at 3 TB clinics in Baltimore
• Assessed effectiveness, acceptability, and cost compared to DOT
• Interviews pre- & post-treatment
• Eligibility: age >18; >2 months of TB Tx remaining
Holzman, et al., Open Forum Infectious Diseases. 2018 Apr 26;5(4):ofy046.

30. VDOT OUTSIDE THE U.S.

31. VDOT for TB Treatment among HIV+
Patients, Tijuana, Mexico
(Funding:UCSD CFAR P30-AI036214;PI: F. Munoz)
Objectives
• To evaluate VDOT for monitoring TB treatment
adherence among HIV/TB co-infected persons
in Tijuana, Mexico
Methods
• HIV-positive patients (N=19) prescribed oral TB medications recruited from
CAPASITS and Tijuana General Hospital
• Eligibility
 >18 years old
 Able to speak Spanish
 No plans to move from Tijuana within the study period
• Data Collection
 Pre- & post-treatment interviews assessed sociodemographics, clinical and
risk factors and VDOT perceptions
 Medical record review for historical sample of patients using DOT (n=50)

32. VDOT
(n=19)
n (%)
In-Person DOT*
(n=50)
n (%)
Age: Mean (SD)
Range
34.1(8.2)
25-56
34.3 (16.0)
21-55
Gender:
Male
Female
13 (68.4)
6 (31.6)
38 (76.0)
12 (24.0)
Treatment Outcome
Continue in treatment
Completion of treatment (Cured)
Lost to follow-up (Abandonment)
Died during TB treatment
Treatment suspended
12 (57.1)
4 (19.0)
2 ( 9.5)
0
1 ( 5.2)
n/a
12 (28.5)
12 (28.5)
6 (14.2)
1 ( 2.3)
Fraction of Expected Doses Observed (mean)** 94.7% 95.5%
TB Treatment Using VDOT among HIV+
Patients, Tijuana, Mexico
*Adherence for historical controls obtained through medical record review for a random sample of patients
treated for TB in the 1 year prior to the study.
**Fraction of expected doses observed = number doses observed divided by number doses expected.

33. n (%)
Overall, I’m “somewhat/very satisfied” with TB treatment using VDOT 17 (100)
I would choose VDOT over DOT if treatment had to be repeated 17 (100)
I would you recommend VDOT to other patients 17 (100)
Confidentiality of VDOT compared to DOT
VDOT > DOT 11 (64.7)
VDOT = DOT 6 (35.3)
Overall, how difficult was the VDOT process?
Somewhat/Very easy 14 (82.4)
Somewhat Difficult 2 (11.7)
Very difficult 1 ( 5.9)
How often did you have problems with the VDOT application?
Never 12 (70.6)
Rarely 5 (29.4)
Satisfaction with VDOT for TB Treatment
among HIV+ Patient , Tijuana, Mexico (n=17)

34. • Methods
• Design: Single arm, prospective cohort
• Sample size: (N=40)
• Eligibility: Age >15 years; DS-TB; >2 months of treatment remaining
• Follow-up: 2 months
• Results
• Median fraction of expected doses observed = 88.4% (IQR:75.8%- 93.7%)
• 71% completed all doses
• 88% of participants would recommend VDOT to other TB patients
• Participants rated VDOT highly, despites some initial technical difficulties
International Journal of Infectious Diseases 2017;65:85–89
VDOT Pilot in Vietnam

35. VDOT Pilot in Kampala, Uganda
Objective
• To evaluate the feasibility of using video directly observed therapy (VDOT) for
supporting TB treatment adherence in Uganda
Setting
• TB clinic in Kampala City, Uganda
Design
• Prospective cohort study
• Eligibility: Age 18-65 yrs; >3 months of TB treatment remaining; only DS-TB
• Followed >3 months
• VDOT patients interviewed pre- & post-treatment

36. Video Submission and Adherence,
Uganda (N=50)
VARIABLE MEASURE
Mean number of days under VDOT intervention per patient, (range) 103 (14-208)
Cumulative total expected videos during VDOT intervention period n=5,150
Cumulative total videos received during VDOT intervention period n=4,231
Cumulative percent videos submitted of total expected 82.2% [95% CI 78%, 85%]
Median number of videos received per patient, (Interquartile range) 89 (52-116)
Median number of videos missed per patient, (Interquartile Range) 15 (7-27)
Median fraction of expected doses observed with VDOT, (IQR) 85% (66-94)

37. P=0.7844 P=0.3650
FEDO by Sex and Age, Uganda

38. P=0.0246
P = 0.3929
FEDO by Phone Ownership and Duration
of Follow-up, Uganda

39. N (%)
Overall, how satisfied are you with the service you have received so far for
your TB treatment?
Very satisfied 45 (90)
How satisfied are you with the clinical care you received by the health
provider at the TB clinic?
Very satisfied 49 (98)
How satisfied were you with your TB treatment monitoring using VDOT?
Very satisfied 46 (92)
How would you compare in-person DOT to VDOT?
VDOT was better than in-person DOT 49 (98)
Would you recommend VDOT to other TB patients?
Yes 50 (100)
Satisfaction with VDOT and Treatment
Services Following Use of VDOT (N=50)

40. VDOT Participant Residence in Relation to Health Facility (H),
Kampala, Uganda

41. Developed and translated into Luganda
(local dialect) by Juliet N. Sekandi
Julius Turinawe & Damalie Nakkonde,
2018
VDOT Patients’ Instructional Materials

42. VDOT for TB Treatment in Prisons in Haiti

43. Challenges in Haitian Prisons and Society
Historical Challenges in Prisons:
• Haiti’s overcrowded correctional facilities create
an environment ripe for TB transmission
• ~1/3 of prisons in Haiti lack full-time health staff
• TB care was not previously offered to persons
living in remote prisons without health staff
• Many barriers and challenges in transferring ill
persons from prisons to treatment sites
Civil Unrest (2019):
• Prevented movement of citizens, including prison
officers and staff, to work, school, stores, medical
clinics, etc. for weeks at a time
• Prisons often remained on “lock down”
Slide Courtesy of Dr. John May and Health Through Walls

44. VDOT in Haitian Prisons - Methods
Intervention:
• VDOT in 5 prisons with no history of providing
TB therapy and DOT in 3 control prisons
• Correctional officers held tablets for VDOT
• Patients were recorded taking their medication
• Health staff at a central facility reviewed videos
and confirmed adherence
• In the event of video failure, correctional
officers reported doses taken or missed
Evaluation:
• Surveys were used to collect demographic and
acceptability data on DOT and VDOT
• Both patients and correctional officers
participated
Source: Dirks, L., Spaulding, A. Video Directly Observed Therapy for Tuberculosis in Haitian Correctional Facilities. Poster. Health Through Walls and Emory University, 2020.

45. Outcomes:
• 67 patients successfully used VDOT at all 5 sites
• Median Adherence
• 85.7% VDOT alone
• 100% VDOT + co-confirmed by correctional officer
• Adherence differed significantly by site
• No treatment failures observed
Challenges:
• Civil unrest causing complete lockdown
• Maintaining a continuous network connection
Conclusions:
• VDOT continued inside the prisons despite unrest and
patients continued to receive their TB medications.
• VDOT facilitated by correctional officers allowed provision
of TB treatment in low resource correctional facilities
• VDOT enabled continuous patient monitoring, treatment
and follow-up
Source: Dirks, L., Spaulding, A. Video Directly Observed Therapy for Tuberculosis in Haitian Correctional Facilities. Poster. Health Through Walls and Emory University, 2020.
VDOT in Haitian Prisons - Results

46. ONGOING VDOT EVALUATIONS
PHILLIPINES
SOUTH AFRICA
KYRGYZSTAN
UKRAINE
VIETNAM
ETHIOPIA
SWAZILAND
PARAGUAY
HAITI
MOZAMBIQUE
TANZANIA
UGANDA
United
States
United
Kingdom

47. WHO Endorses
VDOT in 2017
*Conditional recommendation due to the lack of data from randomized controlled trials.
*
47

48. First Randomized Controlled Trial of VDOT for TB
• Design: 2-arm, parallel, randomized controlled trial
• Location: London and Birmingham, England
• Study Period: 2013-2017
• Eligibility:
• Included – TB patient age >16 years eligible for DOT at participating clinics
• Excluded – can’t charge phone; <2 months treatment remaining
• Primary outcome:
• Proportion of patients with >80% of doses observed
• Data collection:
• Baseline and follow-up interviews
• Adherence records
• Facility cost records
Lancet. 2019;S0140-6736(18):32993-3.

49. Proportion of Subjects who had >80% of
Scheduled Doses Observed by Month
VDOT
DOT

50. Dose
Observations
by TrialArm
Patients are ordered
according to their length
of treatment time
remaining after
randomization.
DOT
VDOT

51. * Any current social risk factor = Homeless, problem drug use, alcohol, prison
0
10
20
30
40
50
60
70
Social risk
factor (any) *
Homeless Prison Drug misuse Alcohol
misuse
Mental
illness
Immigration
concerns
DOT
VOT
Complex cases

52. CDC VDOT Trial, New York City
Burzynski J. Preliminary results of a randomized trial comparing traditional in-person directly observed therapy (DOT) and
video-based DOT for monitoring tuberculosis treatment. 51st Union World Conference on Lung Health; October 20-24, 2020.

53. CDC VDOT Trial, New York City - Results

54. CDC VDOT Trial, New York City -
Conclusions
• Among 173 participants, treatment adherence on VDOT
was non-inferior to DOT with 1.8%-4.1% more doses
observed when VDOT was used
• After the trial period ended, 84% of participants chose to
remain on VDOT
Burzynski J. Preliminary results of a randomized trial comparing traditional in-person directly observed therapy (DOT)
and video-based DOT for monitoring tuberculosis treatment. 51st Union World Conference on Lung Health; October 20-
24, 2020.

55. VDOT FOR LATENT TB
INFECTION TREATMENT

56. LTBI Treatment Options

57. V-MALT: VDOT for Monitoring Adherence
to LTBI Treatment – Aims
(Funding: NIH U01-AI116392; PI: Garfein)
To determine whether completion of latent TB infection
(LTBI) treatment using 3HP* is greater among patients
treated with VDOT versus in-person DOT
To compare treatment acceptability by patients on VDOT
versus in-person DOT and identify factors associated with
acceptability
To measure the cost-effectiveness of VDOT compared to
in-person DOT for monitoring 3HP
*3HP regimen = isoniazid and rifapentine dosed once weekly for 3 months

58. VMALT Study – Methods
Design
• Parallel, randomized controlled trial
Eligibility
• Candidate for 3HP (based on CDC and San Diego County guidelines)
• Age ≥13 years
• Plan to reside in San Diego area for next 4 months
• No physical or cognitive disabilities that preclude VDOT
• Unless household member can assist for the duration of the study
• Not participating in a court ordered alcohol/drug treatment program
Recruitment Sites
• 7 San Diego County HHSA regional TB clinics
• UCSD Student Health Services clinic
• San Ysidro Health Center (FQHC)
Primary Outcome
• Proportion completing treatment (12 observed doses within 16 weeks)

59. V:MALT: Recruitment Flow Diagram
LTBI patients scheduled
N=1902
Walk-in Patients
N=45
Seen at clinic
1365 (70.1%)
Scheduled but not seen
582 (30.6%)
Eligible for study
985 (50.6%)
Not eligible for 3HP or study
380 (27.8%)
Referred to study
185 (9.5%)
Declined referral for study
800 (81.2%)
Enrolled & Randomized
131 (6.7%)
Not consented
38 (20.5%)
Reasons Ineligible for 3HP or Study
Prior 3HP treatment default 52 (13.7%)
Not considered for 3HP 162 (42.6%)
Did not meet other study criteria 97 (26.4%)
Drug treatment program client 69 (18.2%)
Reason Patient Declined Referral for the Study
Refused 3HP 720 (90.0%)
Prefers in-person DOT arm 47 (5.9%)
Prefers VDOT – refuse to randomize 8 (1.0%)
Unwilling to be in a study 25 (3.1%)
Reasons Not Consented for the Study
Decided against 3HP 9 (23.7%)
Time commitment 3 ( 7.9%)
Unwilling to be randomized:
Prefers in-person DOT 8 (21.1%)
Prefers VDOT 3 ( 7.9%)
Deferred treatment 4 (10.5%)
Found to be ineligible for study 1 ( 2.6%)
Transportation problems 1 ( 2.6%)
Too many pills at once for VDOT 1 ( 2.6%)
Not interested/reason unknown 8 (21.1%)
VDOT
(n=68*)
DOT
(n=63)
Reallocated to DOT (n=0)
Lost to Follow-Up (n=1)
Lost to Follow-Up
(n=2)
ITT analysis (n=68)
Restricted analysis (n=67)
ITT analysis (n=63)
Restricted analysis (n=61)
*The first 5 participants were assigned to VDOT prior to starting random assignment.

60. Characteristic
VDOT
(n=68)
DOT
(n=63)
Age, years: mean (range) 33.8 (13-75) 34.2 (14-57)
Female: n (%) 43 (63.2) 37 (58.7)
Race/ethnicity: n (%)
-Asian 18 (26.5) 12 (20.6)
-White 2 (2.9) 4 (6.3)
-Hispanic/Latino 46 (67.6) 41 (65.1)
-Other 2 (2.9) 5 (7.9)
Foreign born: n (%) 52 (76.5) 48 (76.2)
Owned smartphone at baseline: n (%) 64 (97.0) 61 (96.8)
Typical mode of travel to TB clinic (check all that apply)
-Car (includes ride from family/friend) 55 (80.9) 46 (73.0)
-Public transportation or taxi 18 (26.5) 16 (25.4)
-Walk/bike/other 10 (14.7) 9 (14.3)
Usual travel time to the clinic, minutes: mean (SD) 27.0 (24.3) 25.3 (23.7)
How it feels knowing someone will watch you take your meds: n (%)
-Embarrassed/patronized/not trustworthy 2 (2.9) 4 (6.3)
-Cared for/I don't mind it 54 (79.4) 52 (82.5)
V-MALT: Baseline Participant Characteristics

61. 3HP Completion* by Trial Arm
31.1%
26.9%
68.9% 73.1%
*Completion is defined as being observed ingesting 12 doses within 16 weeks.
P=0.697

62. V-MALT: Patient Satisfaction with Treatment
DOT VDOT P-value
Satisfaction with clinical care overall
- Neutral to very dissatisfied
- Somewhat to very satisfied
1 (1.7)
52 (98.3)
0 (0.0)
63 (100)
0.488
Satisfaction with method of
adherence monitoring
- Neutral to very dissatisfied
- Somewhat to very satisfied
8 (13.3)
52 (86.7)
5 (7.9)
58 (92.1)
0.330
Preference if had to redo treatment
- VDOT
- DOT
- No preference
30 (50.0)
17 (28.3)
13 (21.7)
58 (92.1)
1 (1.6)
4 (6.3)
<0.0001
Would recommend my Tx to others
- No
- Yes
10 (16.3)
50 (83.3)
*1 (1.6)
62 (98.4)
0.003
*Response was “no preference”.

63. IS VDOT COST SAVING?

64. V-MALT: Cost by Trial Arm
VDOT
Median (range)
DOT
Median (range)
Personnel $205 ($170 – $340) $236 ($211 – $368)
Device charge* $96 $0
Patient $27 ($20 – $71) $82 ($60 – $212)
Total $328 ($285 – $506) $318 ($272 – $580)
Total (excl. device charge) $240 ($198 – $418) $318 ($272 – $580)
*Device charges include loaned smartphone and phone service.
Device charges may be removed if patient uses their own phone.

65. Cost to Monitor 6 Months of Treatment,
United Kingdom
• DOT
• $7,771 per patient @ five doses/week
• $4,663 per patient @ three doses/week
• VDOT
• $2,243 per patient @ seven doses/week
Story, et al., Lancet. 2019;S0140-6736(18):32993-3.

66. $4,167
$458
$1,293
$174
$0
$500
$1,000
$1,500
$2,000
$2,500
$3,000
$3,500
$4,000
$4,500
SAN DIEGO TIJUANA
COST
PER
CASE
FOR
6
MONTHS
In-Person DOT
VDOT
VDOT Pilot Study: Cost Analysis
In-Person DOT Costs
• Staff salaries and transportation
VDOT Costs
• Staff salaries, transportation, and phone service
• Excludes the cost of the VDOT application

67. • DOT personnel costs included time for patient contact, administrative tasks, and travel.
• VDOT personnel costs included time for DOT visits prior to initiating VDOT, patient VDOT training, administrative tasks,
video observation, and follow-up when expected videos were not received.
• Corporate pricing used for smartphones ($100) and service plans ($54/mth). VDOT app priced at $35/patient/mth.
• Excludes costs for antibiotics, laboratory tests, chest radiographs and clinical exams.
$4609 $4549
$4888
$3212
$5788
$3141 $3179
$3911
$3031 $3137
0
1000
2000
3000
4000
5000
6000
7000
Cost
(USD)
In-person DOT
VDOT
-30% -20% -6% -46%
Total San Diego San Francisco San Joaquin
Imperial
-32%
Cost to Monitor Standard 6-Months of
TB Treatment, California (2015-2016)
Garfein, et al., Emerging Infectious Diseases 2018;24:1806-1815

68. VDOT Trial – Baltimore, MD
Holzman, et al., Open Forum Infectious Diseases. 2018 Apr 26;5(4):ofy046.

69. Environmental Impact of VDOT
[VDOT]

70. Are Digital Adherence
Technology Apps Enough?
• In-person DOT
• Synchronous VOT
• Asynchronous VOT
• 99DOTS
• WisePill
• SMS
• Ingestible sensors
• Observation by AI
• Others
• Physicians
• DOT workers
• Case managers
• Health educators
• Family supporters
• Surveillance
?
?
Patient Inputs Patient Supporters

71. Opportunities in HIV for VDOT?
• LTBI treatment for HIV+
• Establishing treatment routines for ARV initiates
• Supporting patients with low ARV adherence
• Monitoring adherence to PrEP
• Monitoring medication adherence in clinical trials
• Other uses?

72. VDOT for HIV Treatment Adherence
(NIH R21/R33 proposal; PI: Garfein)
• Aim 1: To evaluate the feasibility, acceptability and potential
efficacy of VDOT as an HIV treatment support tool for PLWH
among high-risk groups for poor ART adherence in South
Africa. Groups include:
1) patients starting 2nd or 3rd line ART regimens
2) adolescents at the time of initiating ART to reinforce adherence until
they establish a consistent, independent treatment practice
3) patients with TB and HIV co-infection
• Aim 2: To evaluate the societal costs of VDOT for HIV
treatment support among PLWH.
• Aim 3: To identify modifiable barriers and modifications to
VDOT technology and/or practices that improve the feasibility,
acceptability and adherence to HIV treatment using VDOT
among PLWH.

73. Future directions
• Improving patient support
• Other use cases for VDOT
• Combining technologies to improve outcomes

74. Collaborators
• UC San Diego, School of Medicine: Kevin Patrick, Jazmine Cuevas-Mota , Kelly Collins, Fatima Munoz, Valerie
Mercer, Donald Catanzaro, Maria Luisa Zuniga, Jose Luis Burgos, Timothy Rodwell, Lin Liu, Michelle Bulterys, Erin
South, Diana Do, Constance Benson
• UC San Diego, Qualcomm Institute: Fredric Raab, Phillip Rios, Allison Flick, Mark Sullivan, Ganz Chockalingam,
David McCarter
• San Diego County Health and Human Services Agency
• San Francisco Department of Public Health
• Santa Clara, San Joaquin and Imperial County Health Departments
• California Department of Public Health
• New York City Department of Health: Christine Chuck, Nikolas Mitropoulos, John Soma, Virginia Vasquez-Stewart
• ISESALUD, Tijuana, BC, Mexico: Dra. Liliana Andrade, Dra. Lidia Perez, Dr. Luis Garcia, Dr. Héctor Zepeda Cisneros,
Dr. Gustavo López, Cristhian Colin
• Mexico-US Border Health Commission, BC, Mexico: Dra. Gudelia Rangel Gómez, Carlos Cota, Gabriela Escalante,
• Secretary of Health of the State of Baja California: Dr. Jonathan Figueroa
• Tijuana General Hospital - Integrated Care Services (SAI): Dr. Samuel Navarro
• CAPASITS, Tijuana, BC, Mexico: Dr. Mario Lam
• Center for Connected Health Policy: Mei Kwong, Lois Ritter, Mario Gutierrez
Funded by the National Institutes of Health (R21-AI088326; U01-AI116392; P30-AI036214), Verizon Foundation,
Alliance Healthcare Foundation and California HealthCare Foundation. 74