DigiPrEP: Feasibility and Acceptability of Digital Pills to Monitor PrEP Adherence in MSM With Substance Use

• Sponsor: Peter Chai (Other)
• Overall Status: Completed
• CT.gov ID: NCT03842436
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 16
• Location: 1
• Arm: 1
• Actual Duration (Months): 18.7
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study deploys a novel digital pill with Emtricitabine/Tenofovir (TDF/FTC) among MSM with substance use to monitor PrEP adherence. The investigators will enroll N=15 HIV uninfected MSM with self reported substance use who are on PrEP or initiating PrEP to use digital pills over encapsulating TDF/FTC for 3 months. The investigators will assess the feasibility of using digital pills in this study population as well as understand the acceptability of digital pills for adherence measurement using semi-structured individual interviews. Additionally, the investigators will measure adherence over time, as well as episodes of suboptimal PrEP adherence.

Condition or Disease	Intervention/Treatment	Phase
HIV/AIDS; Substance Use Disorders; Adherence, Medication	Device: Digital pill; Drug: Truvada	Phase 4

Detailed Description

Eligible study participants will be screened and enrolled at Fenway Health (Boston, MA). Participants will complete a quantitative assessment on their history fo substance use, sexual risk and PrEP adherence, and be trained to use the digital pill for 90 days and instructed to take PrEP daily during the course of the study. Participants will return each month for a study visit to assess their use of the technology. At study visit 1 and 3, we will obtain dried blood spots (DBS) to measure drug levels and to confirm adherence detected by the digital pill. The investigators will also obtain drugs of abuse screens from DBS. At the final study visit (3 months), participants will undergo a semi-structured qualitative interview to understand the user response to digital pills.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single group pilot demonstration projectSingle group pilot demonstration project
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Feasibility and Acceptability of Digital Pills to Monitor PrEP Adherence in MSM With Substance Use
• Actual Study Start Date: Oct 1, 2018
• Actual Primary Completion Date: Apr 22, 2020
• Actual Study Completion Date: Apr 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Digital Pills Digital Pills containing Truvada ingested once daily as PrEP	Device: Digital pill; Digital pills over encapsulating Truvada; Other Names: eTectRx ID Cap ; Drug: Truvada; Truvada prescribed with digital pills for PrEP

Outcome Measures

Primary Outcome Measures

1. Feasibility of Digital Pills to Measure PrEP Adherence [Months 1, 2, and 3]

   Participants' engagement with the digital pill system (DPS) was measured over the 90-day study period. The percentages for the total expected ingestions recorded by DPS each month were compared.

Secondary Outcome Measures

1. Digital Pill Performance - Number of Recorded Ingestions [Months 1, 2, and 3]

   The total number recorded ingestions recorded by the digital pill system (DPS) - which included both the number of Reader-detected and manually-reported ingestions - was collected. The Reader-detected ingestions count was used to reflect the number of times the DPS was operated correctly. Successful DPS operation was defined as ingestion of a digital pill, proper use of the wearable Reader, and confirmation of the ingestion on both the Reader and the app. Cumulative data collected at months 1, 2, and 3 are reported in the data table below.

2. Digital Pill Performance - System Accuracy [Months 1, 2, and 3]

   Accuracy of the digital pill system (DPS) in measuring PrEP adherence. To analyze the performance of the DPS, the ground truth of PrEP ingestion events was defined as the pill counts obtained each month (i.e., the number of unused pills returned, subtracted from the number of pills previously dispensed). The number of DPS-recorded ingestions - which included the number of both Reader-detected and manually-reported ingestions - was compared with the aggregate pill count at each monthly timepoint; this was defined as the overall performance metric for the DPS. Cumulative data collected at months 1, 2, and 3 are reported in the data table below.

3. Digital Pill Performance - Manually Reported Ingestions [Months 1, 2, and 3]

   The total number of manually reported ingestions was collected. The percentages for instances of manually reported ingestions were calculated. The two instances for manually recording ingestions included, a lack of engagement with the Reader or failure to use the Reader properly, and when reported ingestion was not detected by the Reader despite supporting use metrics indicating proper Reader use. Cumulative data collected at months 1, 2, and 3 are reported in the data table below.

4. Digital Pill Performance - Successful Operation of System [Months 1, 2, and 3]

   The total number of instances in which ingestions were successfully detected by the Reader (i.e., the radio frequency emitter was activated, and the ingestion was recorded by the DPS) was collected. The total number of instances in which manually reported ingestions were not detected by the Reader, despite supporting use metrics (e.g., accelerometer data) indicating proper Reader use was also collected. These counts were combined and interpreted as the number of times that the DPS was operated correctly. Cumulative data collected at months 1, 2, and 3 are reported in the data table below.

5. Dried Blood Spot Correlation With Digital Pill Adherence [Months 1 and 3]

   We dichotomized TFV-DP levels using a cutoff of ≥700 fmol/punch to indicate at least four doses of PrEP ingested per week. Using TFV-DP in DBS <700 vs ≥700 fmol/punch as a dichotomous variable, and considering the granular continuous adherence data from the digital pill, we then calculated a point biserial correlation between TFV-DP in DBS and digital pill adherence. Additionally, drug concentrations of tenofovir diphosphate as measured in dried blood spot collection at months one and three were compared to DPS-recorded PrEP adherence.

Other Outcome Measures

1. Number of Participants That Completed Qualitative Interview to Evaluate Acceptability of Digital Pills [Month 3]

   Acceptability was assessed via individual, semi-structured, qualitative exit interviews conducted at the end of the 90-day study period. The qualitative interview guide was grounded in the Technology Acceptance Model. Questions explored participants' experiences using the digital pill system (DPS), including facilitators and barriers to use, engagement with the technology, and willingness to use the DPS long-term.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. MSM (cisgender male)

2. Self-reported use of non-alcohol substances of abuse in past 6 months

3. Currently taking PrEP

4. Has qualifying laboratory tests (Cr, hepatitis B immunization, STI testing and syphilis)

5. Age 18 or older

Exclusion Criteria:

1. Does not speak English

2. HIV positive

3. Identifies as transgender

4. Estimated creatinine clearance <60ml/min

5. Active hepatitis B treatment

6. Does not own a smartphone

7. Taking proton pump inhibitors

8. History of Crohn's disease or ulcerative colitis

9. History of bowel surgery, gastric bypass, bowel stricture

10. History of GI malignancy or radiation to abdomen

11. Unable/unwilling to ingest digital pill

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fenway Health	Boylston	Massachusetts	United States	02215

Sponsors and Collaborators

• Peter Chai
• Gilead Sciences

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 5, 2019
• Statistical Analysis Plan - Sep 3, 2021

More Information

Publications

None provided.

• Responsible Party: Peter Chai, Affiliated Faculty, Fenway Community Health
• ClinicalTrials.gov Identifier: NCT03842436
• Other Study ID Numbers: 1087733
• First Posted: Feb 15, 2019
• Last Update Posted: Dec 3, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Peter Chai, Affiliated Faculty, Fenway Community Health: PrEP; Substance Use Disorder; Digital Pills; Medication Adherence
• Additional relevant MeSH terms: Substance-Related Disorders; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Period Title: Overall Study
STARTED	16
COMPLETED	15
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Overall Participants	15
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	32
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	15 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 26.7%
Not Hispanic or Latino	11 73.3%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	10 66.7%
Black / African American	1 6.7%
Asian	1 6.7%
More than one race	2 13.3%
Other	1 6.7%
Region of Enrollment (Count of Participants)
United States	15 100%
Education (Count of Participants)
Some college	2 13.3%
College degree	7 46.7%
Graduate degree/professional	6 40%
Sexual Orientation (Count of Participants)
Homosexual or gay	13 86.7%
Bisexual	2 13.3%
STI in prior 12 month (Count of Participants)
Yes	10 66.7%
No	5 33.3%
Reported substance use (Count of Participants)
Alcohol	14 93.3%
Marijuana	10 66.7%
Stimulants	7 46.7%
Hallucinogens	4 26.7%
Other (poppers, amyl nitrate)	7 46.7%
Prescribed PrEP (Count of Participants)
Yes	14 93.3%
No	1 6.7%
Nonadherent to PrEP in prior 2 weeks (self-report) (Count of Participants)
Yes	3 20%
No	11 73.3%

Outcome Measures

1. Primary Outcome

Title	Feasibility of Digital Pills to Measure PrEP Adherence
Description	Participants' engagement with the digital pill system (DPS) was measured over the 90-day study period. The percentages for the total expected ingestions recorded by DPS each month were compared.
Time Frame	Months 1, 2, and 3

Outcome Measure Data

Analysis Population Description

One participant was temporarily lost to follow-up, so they were excluded from analysis. In Month 1, the total number of DPS-recorded ingestion events (411) exceeded the total expected ingestion events from pill counts (402), as a result of one participant returning nine more unused pills than anticipated at the end of the month. The total expected ingestions for Month 1 is listed as 411 in the table below for clarity.

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Measure Participants	14
Measure Expected ingestions per pill counts	1192
Month 1: Total ingestions recorded by DPS	411
Month 2: Total ingestions recorded by DPS	368
Month 3: Total ingestions recorded by DPS	320

2. Secondary Outcome

Title	Digital Pill Performance - Number of Recorded Ingestions
Description	The total number recorded ingestions recorded by the digital pill system (DPS) - which included both the number of Reader-detected and manually-reported ingestions - was collected. The Reader-detected ingestions count was used to reflect the number of times the DPS was operated correctly. Successful DPS operation was defined as ingestion of a digital pill, proper use of the wearable Reader, and confirmation of the ingestion on both the Reader and the app. Cumulative data collected at months 1, 2, and 3 are reported in the data table below.
Time Frame	Months 1, 2, and 3

Outcome Measure Data

Analysis Population Description

One participant was temporarily lost to follow-up.

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Measure Participants	14
Measure Recorded ingestions	1099
Reader-detected ingestions	922
Manually reported ingestions	177

3. Secondary Outcome

Title	Digital Pill Performance - System Accuracy
Description	Accuracy of the digital pill system (DPS) in measuring PrEP adherence. To analyze the performance of the DPS, the ground truth of PrEP ingestion events was defined as the pill counts obtained each month (i.e., the number of unused pills returned, subtracted from the number of pills previously dispensed). The number of DPS-recorded ingestions - which included the number of both Reader-detected and manually-reported ingestions - was compared with the aggregate pill count at each monthly timepoint; this was defined as the overall performance metric for the DPS. Cumulative data collected at months 1, 2, and 3 are reported in the data table below.
Time Frame	Months 1, 2, and 3

Outcome Measure Data

Analysis Population Description

One participant was temporarily lost to follow-up, so they were excluded from the analysis.

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Measure Participants	14
Measure Expected ingestions based on pill counts	1192
Number (95% Confidence Interval) [percentage of ingestions DPS recorded]	92

4. Secondary Outcome

Title	Digital Pill Performance - Manually Reported Ingestions
Description	The total number of manually reported ingestions was collected. The percentages for instances of manually reported ingestions were calculated. The two instances for manually recording ingestions included, a lack of engagement with the Reader or failure to use the Reader properly, and when reported ingestion was not detected by the Reader despite supporting use metrics indicating proper Reader use. Cumulative data collected at months 1, 2, and 3 are reported in the data table below.
Time Frame	Months 1, 2, and 3

Outcome Measure Data

Analysis Population Description

One participant was temporarily lost to follow-up.

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Measure Participants	14
Measure Manually-reported ingestions	177
Lack of engagement with the Reader or failure to use Reader properly	158
Instances where reported ingestion was not detected by the Reader despite proper Reader use	19

5. Secondary Outcome

Title	Digital Pill Performance - Successful Operation of System
Description	The total number of instances in which ingestions were successfully detected by the Reader (i.e., the radio frequency emitter was activated, and the ingestion was recorded by the DPS) was collected. The total number of instances in which manually reported ingestions were not detected by the Reader, despite supporting use metrics (e.g., accelerometer data) indicating proper Reader use was also collected. These counts were combined and interpreted as the number of times that the DPS was operated correctly. Cumulative data collected at months 1, 2, and 3 are reported in the data table below.
Time Frame	Months 1, 2, and 3

Outcome Measure Data

Analysis Population Description

One participant was temporarily lost to follow-up.

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Measure Participants	14
Measure Ingestions successfully detected by DPS	941
Reader-detected digital pill ingestions that activated radio frequency emitter	922
Manually reported digital pill ingestions with supporting use metrics indicating proper Reader use	19

6. Secondary Outcome

Title	Dried Blood Spot Correlation With Digital Pill Adherence
Description	We dichotomized TFV-DP levels using a cutoff of ≥700 fmol/punch to indicate at least four doses of PrEP ingested per week. Using TFV-DP in DBS <700 vs ≥700 fmol/punch as a dichotomous variable, and considering the granular continuous adherence data from the digital pill, we then calculated a point biserial correlation between TFV-DP in DBS and digital pill adherence. Additionally, drug concentrations of tenofovir diphosphate as measured in dried blood spot collection at months one and three were compared to DPS-recorded PrEP adherence.
Time Frame	Months 1 and 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Measure Participants	15
Measure Paired DBS samples	22
Point-biserial correlation	0.58
Pearson's correlation for month one	0.85
Pearson's correlation for month three	0.75

7. Other Pre-specified Outcome

Title	Number of Participants That Completed Qualitative Interview to Evaluate Acceptability of Digital Pills
Description	Acceptability was assessed via individual, semi-structured, qualitative exit interviews conducted at the end of the 90-day study period. The qualitative interview guide was grounded in the Technology Acceptance Model. Questions explored participants' experiences using the digital pill system (DPS), including facilitators and barriers to use, engagement with the technology, and willingness to use the DPS long-term.
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

Qualitative user experience data were collected via interviews from the 15 participants who completed the study.

Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
Measure Participants	15
Count of Participants [Participants]	15 100%

Adverse Events

Time Frame	3 months
Arm/Group Title	Digital Pills
Arm/Group Description	Digital Pills containing Truvada ingested once daily as PrEP Digital pill: Digital pills over encapsulating Truvada Truvada: Truvada prescribed with digital pills for PrEP
All Cause Mortality
	Digital Pills
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Digital Pills
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Digital Pills
	Affected / at Risk (%)	# Events
Total	0/15 (0%)

Limitations/Caveats

(1) Most participants were White and well-educated, limiting generalizability. (2) Opportunities for technical DPS improvements arose during the study, which required some participants to temporarily manually record doses. (3) The assay utilized for TFV-DP has not been cross-validated and may result in errors in assayed concentration of TFV-DP. (4) Reliance on pill counts may have decreased the measured accuracy of the DPS among participants who did not return unused pills each month.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.