HIV/AIDS
Conditions
Keywords
ART Adherence, Reminders, Behavioral Economics, Viral Suppression, Long-term Adherence, Routines, Habit Formation
Brief summary
The study will test the feasibility and acceptability of using text messages and behavioral economics-based incentives to support anchoring Anti-Retroviral Therapy (ART) adherence to an existing routine in order to improve long-term ART medication adherence. The intervention phase of the three-phased study will constitute the pilot RCT. A sample of 150 clients who have initiated ART in the preceding three months will be randomized to either usual care (C = 50) or one of the two INMIND intervention groups (daily text message reminders with or without incentives) for three months (T1 = 50; T2=50). Subsequently, behavioral persistence will be evaluated for six months post-intervention. Assessments will be conducted at baseline, month 3, and month 9. The primary outcomes are 1) electronically measured mean medication adherence during the intervention and 2) six months post intervention, along with 3) timeliness of medication adherence during the intervention and 4) six months post-intervention.
Detailed description
Adherence of Anti-Retroviral Therapy (ART) among HIV-infected patients initiating treatment (treatment initiators) in Sub-Saharan Africa has remained low, even though the number of treatment initiators has increased in recent years. Lack of retention in care and low adherence in the first year of ART treatment are substantial barriers to virologic suppression. The current R34 study tests a novel approach for improving long-term ART adherence among treatment initiators by turning adherence into a behavioral routine. This is done in two ways: 1) anchoring ART adherence to an existing routine, and 2) providing more immediate rewards and increasing the salience through reminder messages. Insights from behavioral economics suggest that such an intervention may be particularly effective for people with present bias (those who have a tendency to give in to short-term temptation at the cost of more long-term benefits) and lack of salience (where over time, the choice of target behavior is overshadowed by more pressing needs of daily life) which have been found to be prevalent among people living with chronic medical conditions from past studies. The intervention will be tested through a pilot RCT, wherein 150 adult clients will be randomly assigned to three groups. The first intervention group would receive daily text messages that reinforce routine formation information provided to all participants (across the three groups). The second intervention group will receive the text messages, and additionally be eligible for a prize drawing based on timely ART adherence, at each monthly clinic visit. The control group will receive care as usual, consisting of routine formation information as well as adherence counseling. The intervention will last three months, with a six-month post-intervention follow up period. All participants will receive MEMS caps to record adherence, and will complete assessments over nine months (baseline, post-intervention, and six months post-intervention). The Specific Aim of the intervention phase of the study is to test the preliminary effectiveness of the intervention, including the relative effectiveness of the two different implementation approaches. This is preceded by the formative phase, with the Specific Aim of developing the intervention parameters. The intervention phase is succeeded by the adaptation phase, whose Specific Aim is to collect data in preparation for a subsequent R01 application.
Interventions
BEHAVIORALDaily Text Messages
Participants will receive daily text message reminders to use their routine behavior to trigger medication adherence.
Participants will be eligible to draw a prize if they take their medication within +/- one hour of the stated existing routine to which pill-taking is anchored on at least 70% of days between recruitment and the 3-month study visit.
Sponsors
National Institute of Mental Health (NIMH)
Mildmay Uganda Limited
Arizona State University
RAND
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The investigator and outcomes assessor will be blinded to treatment assignment of study participants.
Intervention model description
A pilot randomized controlled trial with two intervention arms and a control group, that will receive intervention for three months with follow-on assessment for six months after the intervention period ends.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female clients age 18 and older. * Started ART at Mildmay or another clinic within the preceding three months but have since been receiving care at Mildmay. * Able to speak and understand either English or Luganda. * Have their own cell phone or have consistent access to someone else's phone. * Willing to receive daily text messages for the 3 months of intervention duration. * Willing and able to use the MEMS caps distributed for adherence verification for the duration of the study.
Exclusion criteria
* Not mentally fit to consent. * Language other than Luganda or English. * Not willing to consistently use the MEMS caps device for adherence measurement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Pills Taken as Prescribed Over the Intervention Period (Baseline - Month 3) | Three months | MEMS-data was collected continuously over the course of the three-month intervention period allowing us to investigate mean adherence. Only one of the ART medications was used to calculate the primary adherence variable (# of actual bottle openings / # of prescribed bottle openings). |
| Proportion of Pills Taken as Prescribed Over the Post-intervention Period (Months 4-9) | Six months post-intervention | MEMS-data was collected continuously over the course of the six-month post intervention period allowing for the investigation of post-intervention mean adherence. Only one of the ART medications was used to calculate the primary adherence variable (# of actual bottle openings / # of prescribed bottle openings). |
| Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Intervention Period (Baseline - Month 3) | Three months | A novel measure of routine adherence (that it is explicitly based on the temporal pattern of pill-taking), calculated as the fraction of scheduled pills taken within a one-hour window around the typical time that participants report completing their existing routine behavior that anchors their pill-taking, was calculated. This measure provides an objective way for determining behavioral automaticity of pill-taking. |
| Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Post-Intervention Period (Months 4-9) | Six months post-intervention | This measure would be calculated as a fraction of scheduled pills taken within a one-hour window around the typical time that participants report completing their existing routine behavior that anchors their pill-taking, for all visits made post-intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retention in Care | Month 9 | Retention in care was measured as the fraction of participants recruited who are still active clients at the clinic at month 9. |
| Change in Viral Suppression Status | Month 9 | HIV RNA (viral load) was the secondary outcome measure. For each participant, viral loads taken just prior to baseline and viral loads taken just after month-9 were compared; if participant was virally suppressed (with \< 200 copies of HIV per millilitre (mL) of blood) at baseline, but had a viral load of \>= 200 copies/mL after month-9, then the indicator was assigned -1; if there was no change in viral suppression status (i.e., if participant either had \>= 200 copies of virus/mL at baseline and month-9 OR if participant had \< 200 copies/mL at baseline and month-9), then the indicator was assigned 0. If, however, the participant's viral load went from \>= 200 copies/mL at baseline to \< 200 copies/mL after month-9, then the indicator was assigned 1. |
Countries
Uganda
Participant flow
Recruitment details
In a randomized, parallel controlled trial, a sample of 166 participants who met the inclusion criteria were recruited at Mildmay Uganda between October, 2021 and April, 2022. Participants were excluded if a) they did not own an phone, b) they started ARTs \> 3 months prior to enrollment, c) they were not at Mildmay general or planned to transfer our during the study period, d) could not offer informed consent, or e) could not commit to study activities
Pre-assignment details
After recruitment but prior to random assignment and baseline assessment, enrolled participants were given a MEMS cap to screen for non-use (recorded adherence \< 30% over a month). Of 166 enrolled, 3 participants were excluded due to MEMS non-use, 3 did not return for baseline, and 1 withdrew consent at baseline, leaving 159 participants to randomize. Of these, 2 in the control group and 1 in the Messages group withdrew consent after baseline and thus their data are not reported in the flow.
Participants by arm
| Arm | Count |
|---|---|
| Control This arm will receive care as usual, including the adherence support mechanisms that are part of usual care practices. At recruitment participant will be explained the importance of pill-taking. All participants (including in the control group) will receive a leaflet containing detailed information on how to establish healthy medication-taking routines. Finally, clinic staff will counsel participants on how to select an already established routine behavior that occurs at roughly the same time each day that forms the basis of their implementation plan. | 49 |
| Intervention Group Receiving Messages (Messages Group) Participants will receive the same information as those in the Control Group, but in addition, receive the Daily Text Message Intervention for the first three months after baseline.
Daily Text Messages: Participants will receive daily text message reminders to use their routine behavior to trigger medication adherence. | 49 |
| Intervention Group Receiving Messages and Incentives (Incentives Group) Participants will receive the same information as the Control group. Additionally, they will receive the Daily Text Message Intervention and will be eligible for incentivization based on timely ART adherence for the first three months after baseline.
Daily Text Messages: Participants will receive daily text message reminders to use their routine behavior to trigger medication adherence.
Incentivization based on timely ART adherence: Participants will be eligible to draw a prize if they take their medication within +/- one hour of the stated existing routine to which pill-taking is anchored on at least 70% of days between recruitment and the 3-month study visit. | 58 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | Dropped out | 1 | 2 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 | 5 |
| Overall Study | Transferred out of clinic | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Control | Intervention Group Receiving Messages (Messages Group) | Intervention Group Receiving Messages and Incentives (Incentives Group) | Total |
|---|---|---|---|---|
| Age, Continuous | 33.06 years STANDARD_DEVIATION 8.33 | 33.57 years STANDARD_DEVIATION 8.9 | 34.84 years STANDARD_DEVIATION 11.34 | 33.9 years STANDARD_DEVIATION 9.69 |
| % disclosed HIV status | 43 Participants | 40 Participants | 47 Participants | 130 Participants |
| % employed at baseline | 35 Participants | 40 Participants | 46 Participants | 121 Participants |
| % food insecure | 11 Participants | 13 Participants | 12 Participants | 36 Participants |
| % married (or partnered) | 31 Participants | 23 Participants | 33 Participants | 87 Participants |
| Monthly income | 59.20 USD STANDARD_DEVIATION 119.29 | 78.02 USD STANDARD_DEVIATION 81.71 | 72.95 USD STANDARD_DEVIATION 116.55 | 70.10 USD STANDARD_DEVIATION 107.26 |
| Number of children | 2.37 children STANDARD_DEVIATION 2.13 | 2.94 children STANDARD_DEVIATION 3.27 | 2.70 children STANDARD_DEVIATION 2.16 | 2.67 children STANDARD_DEVIATION 2.55 |
| % primary education or less | 21 Participants | 24 Participants | 25 Participants | 70 Participants |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment Uganda | 49 participants | 49 participants | 58 participants | 156 participants |
| Sex: Female, Male Female | 32 Participants | 31 Participants | 40 Participants | 103 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 18 Participants | 53 Participants |
| Travel to clinic: Cost | 3.79 USD STANDARD_DEVIATION 3.72 | 3.52 USD STANDARD_DEVIATION 3.49 | 3.33 USD STANDARD_DEVIATION 2.39 | 3.53 USD STANDARD_DEVIATION 3.2 |
| Travel to clinic: Time (Hrs) | 1.14 hours STANDARD_DEVIATION 0.62 | 1.19 hours STANDARD_DEVIATION 0.91 | 1.41 hours STANDARD_DEVIATION 2.59 | 1.25 hours STANDARD_DEVIATION 1.68 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 51 | 1 / 50 | 0 / 58 |
| other Total, other adverse events | 0 / 51 | 0 / 50 | 0 / 58 |
| serious Total, serious adverse events | 0 / 51 | 0 / 50 | 0 / 58 |
Outcome results
Primary
Proportion of Pills Taken as Prescribed Over the Intervention Period (Baseline - Month 3)
MEMS-data was collected continuously over the course of the three-month intervention period allowing us to investigate mean adherence. Only one of the ART medications was used to calculate the primary adherence variable (# of actual bottle openings / # of prescribed bottle openings).
Time frame: Three months
Population: Includes all enrolled participants with at least one day's adherence data from the MEMS cap between baseline and month 3 visits (n = 155).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Control | Proportion of Pills Taken as Prescribed Over the Intervention Period (Baseline - Month 3) | 0.860 Proportion of pills taken as prescribed | Standard Error 0.027 |
| Intervention Group Receiving Messages (Messages Group) | Proportion of Pills Taken as Prescribed Over the Intervention Period (Baseline - Month 3) | 0.916 Proportion of pills taken as prescribed | Standard Error 0.03 |
| Intervention Group Receiving Messages and Incentives (Incentives Group) | Proportion of Pills Taken as Prescribed Over the Intervention Period (Baseline - Month 3) | 0.914 Proportion of pills taken as prescribed | Standard Error 0.028 |
Comparison: The analyses utilized control as the reference group, and thus, the values reported include control mean and standard error as the reference value (derived from an ordinary least squared regression without controls). The results for the intervention groups are derived from the multiple regression model that controlled for other participant characteristics, including demographics, intrinsic motivation and habit strength at baseline.p-value: 0.056ANCOVA
Comparison: The analyses utilized control as the reference group, and thus, the values reported include control mean and standard error as the reference value (derived from an ordinary least squared regression without controls). The results for the intervention groups are derived from the multiple regression model that controlled for other participant characteristics, including demographics, intrinsic motivation and habit strength at baseline.p-value: 0.062ANCOVA
Primary
Proportion of Pills Taken as Prescribed Over the Post-intervention Period (Months 4-9)
MEMS-data was collected continuously over the course of the six-month post intervention period allowing for the investigation of post-intervention mean adherence. Only one of the ART medications was used to calculate the primary adherence variable (# of actual bottle openings / # of prescribed bottle openings).
Time frame: Six months post-intervention
Population: Includes all enrolled participants with at least one day's adherence data from the MEMS cap between months 4-9 (n = 135).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Control | Proportion of Pills Taken as Prescribed Over the Post-intervention Period (Months 4-9) | 0.800 Proportion of pills taken as prescribed | Standard Error 0.029 |
| Intervention Group Receiving Messages (Messages Group) | Proportion of Pills Taken as Prescribed Over the Post-intervention Period (Months 4-9) | 0.842 Proportion of pills taken as prescribed | Standard Error 0.038 |
| Intervention Group Receiving Messages and Incentives (Incentives Group) | Proportion of Pills Taken as Prescribed Over the Post-intervention Period (Months 4-9) | 0.835 Proportion of pills taken as prescribed | Standard Error 0.032 |
Comparison: The analyses utilized control as the reference group, and thus, the values reported include control mean and standard error as the reference value (derived from an ordinary least squared regression without controls). The results for the intervention groups are derived from the multiple regression model that controlled for other participant characteristics, including demographics, intrinsic motivation and habit strength at baseline.p-value: 0.364ANCOVA
Comparison: The analyses utilized control as the reference group, and thus, the values reported include control mean and standard error as the reference value (derived from an ordinary least squared regression without controls). The results for the intervention groups are derived from the multiple regression model that controlled for other participant characteristics, including demographics, intrinsic motivation and habit strength at baseline.p-value: 0.409ANCOVA
Primary
Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Intervention Period (Baseline - Month 3)
A novel measure of routine adherence (that it is explicitly based on the temporal pattern of pill-taking), calculated as the fraction of scheduled pills taken within a one-hour window around the typical time that participants report completing their existing routine behavior that anchors their pill-taking, was calculated. This measure provides an objective way for determining behavioral automaticity of pill-taking.
Time frame: Three months
Population: Includes all enrolled participants with at least one day's adherence data from the MEMS cap between baseline and month 3 visits (n = 155).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Control | Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Intervention Period (Baseline - Month 3) | 0.685 Proportion of pills taken in time window | Standard Error 0.041 |
| Intervention Group Receiving Messages (Messages Group) | Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Intervention Period (Baseline - Month 3) | 0.755 Proportion of pills taken in time window | Standard Error 0.05 |
| Intervention Group Receiving Messages and Incentives (Incentives Group) | Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Intervention Period (Baseline - Month 3) | 0.81 Proportion of pills taken in time window | Standard Error 0.05 |
Comparison: The analyses utilized control as the reference group, and thus, the values reported include control mean and standard error as the reference value (derived from an ordinary least squared regression without controls). The results for the intervention groups are derived from the multiple regression model that controlled for other participant characteristics, including demographics, intrinsic motivation and habit strength at baseline.p-value: 0.158ANCOVA
Comparison: The analyses utilized control as the reference group, and thus, the values reported include control mean and standard error as the reference value (derived from an ordinary least squared regression without controls). The results for the intervention groups are derived from the multiple regression model that controlled for other participant characteristics, including demographics, intrinsic motivation and habit strength at baseline.p-value: 0.017ANCOVA
Primary
Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Post-Intervention Period (Months 4-9)
This measure would be calculated as a fraction of scheduled pills taken within a one-hour window around the typical time that participants report completing their existing routine behavior that anchors their pill-taking, for all visits made post-intervention.
Time frame: Six months post-intervention
Population: Includes all enrolled participants with at least one day's adherence data from the MEMS cap between months 4-9 (n = 135).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Control | Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Post-Intervention Period (Months 4-9) | 0.546 Proportion of pills taken in time window | Standard Error 0.047 |
| Intervention Group Receiving Messages (Messages Group) | Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Post-Intervention Period (Months 4-9) | 0.573 Proportion of pills taken in time window | Standard Error 0.066 |
| Intervention Group Receiving Messages and Incentives (Incentives Group) | Proportion of Pills Taken Within +/- 1 Hour of the Anchor Time Over the Post-Intervention Period (Months 4-9) | 0.680 Proportion of pills taken in time window | Standard Error 0.064 |
Comparison: The analyses utilized control as the reference group, and thus, the values reported include control mean and standard error as the reference value (derived from an ordinary least squared regression without controls). The results for the intervention groups are derived from the multiple regression model that controlled for other participant characteristics, including demographics, intrinsic motivation and habit strength at baseline.p-value: 0.654ANCOVA
Comparison: The analyses utilized control as the reference group, and thus, the values reported include control mean and standard error as the reference value (derived from an ordinary least squared regression without controls). The results for the intervention groups are derived from the multiple regression model that controlled for other participant characteristics, including demographics, intrinsic motivation and habit strength at baseline.p-value: 0.035ANCOVA
Secondary
Change in Viral Suppression Status
HIV RNA (viral load) was the secondary outcome measure. For each participant, viral loads taken just prior to baseline and viral loads taken just after month-9 were compared; if participant was virally suppressed (with \< 200 copies of HIV per millilitre (mL) of blood) at baseline, but had a viral load of \>= 200 copies/mL after month-9, then the indicator was assigned -1; if there was no change in viral suppression status (i.e., if participant either had \>= 200 copies of virus/mL at baseline and month-9 OR if participant had \< 200 copies/mL at baseline and month-9), then the indicator was assigned 0. If, however, the participant's viral load went from \>= 200 copies/mL at baseline to \< 200 copies/mL after month-9, then the indicator was assigned 1.
Time frame: Month 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Viral Suppression Status | 0.03 indicator score | Standard Deviation 0.175 |
| Intervention Group Receiving Messages (Messages Group) | Change in Viral Suppression Status | 0 indicator score | Standard Deviation 0.039 |
| Intervention Group Receiving Messages and Incentives (Incentives Group) | Change in Viral Suppression Status | 0 indicator score | Standard Deviation 0.035 |
Comparison: The analyses compared the change in viral suppression status of the participants from baseline to month 9. For each participant, we derived the change in viral suppression status by subtracting two binary variables - one indicating whether the participant was virally suppressed at baseline (based on their chart records from around 3 months prior to baseline) and the other indicating whether the participant was virally suppressed at around month 9 of the study.p-value: 0.5468t-test, 2 sided
Comparison: The analyses compared the change in viral suppression status of the participants from baseline to month 9. For each participant, we derived the change in viral suppression status by subtracting two binary variables - one indicating whether the participant was virally suppressed at baseline (based on their chart records from around 3 months prior to baseline) and the other indicating whether the participant was virally suppressed at around month 9 of the study.p-value: 0.5255t-test, 2 sided
Secondary
Retention in Care
Retention in care was measured as the fraction of participants recruited who are still active clients at the clinic at month 9.
Time frame: Month 9
Population: All participants that consented to participate and were randomized to treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Retention in Care | 48 Participants |
| Intervention Group Receiving Messages (Messages Group) | Retention in Care | 50 Participants |
| Intervention Group Receiving Messages and Incentives (Incentives Group) | Retention in Care | 57 Participants |