Adherence, Medication, HIV-1-infection
Conditions
Brief summary
This is a randomized study for participants treated with tenofovir-based antiretroviral drug regimens with a history of suboptimal adherence (detectable HIV RNA twice over the last year). Eligible participants are enrolled, receive routine adherence counseling and are randomized to receive an AdhereTech smart pill bottle or not (open label). The smart pill bottle quantitates the number of tenofovir-containing pills taken and sends this to a centralized server; if a dose is missed, the participant is contacted by either phone or text. Participants are assessed at baseline and weeks 4, 8, and 12 for tenofovir diphosphate (TFV-DP) levels (by plasma and dried red blood cell spots), HIV RNA level, and adherence using a standardized questionnaire. Primary outcome is change in TFV-DP levels from baseline in the 2 groups.
Interventions
DEVICEAdheretech smart bottle
A smart pill bottle that measures the exact number of pills in the bottle in real-time, sends this HIPAA-compliant data to a central server, and based on the results, can remind participants to take their medication through a phone call or text message.
BEHAVIORALRoutine adherence counseling
Participants will be provided with routine adherence counseling
Sponsors
AdhereTech
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-infected * Taking a tenofovir-containing antiretroviral regimen for HIV treatment * Documented suboptimal adherence (2 HIV RNA levels documented above the level of detection, i.e. not suppressed, on 2 occasions over the prior 52 weeks
Exclusion criteria
* Plans to change the current HIV drug regimen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Tenofovir Diphosphate (TFV-DP) Drug Levels | Baseline and Week 12 | Using dried blood spots from red blood cells, TFV-DP levels will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Completing the 12 Week AdhereTech Bottle Intervention Compared to the Routine Counseling Only Group. | Week 12 | Feasibility of using the AdhereTech Smart Pill Bottles in individuals living with HIV as measured by the proportion of participants that complete the study compared between arms. A statistically lower proportion in the AdhereTech bottle arm compared to the routine counseling arm would suggest use of the bottle is not feasible. |
| Change in Quantitative HIV Viral Load | Baseline and Week 12 | Comparative changes in quantitative HIV viral load between baseline and Week 12 in the AdhereTech bottle arm versus the routine counseling only arm. |
| Number of Participants With HIV RNA ≥ 20 Copies/mL at Baseline That Had a Decrease in HIV RNA to < 20 Copies/mL at Week 12 in the AdhereTech Bottle Arm Versus the Routine Counseling Only Arm. | Baseline and Week 12 | This is a measure of qualitative HIV RNA outcome. The number of participants converting from detectable (HIV RNA ≥ 20 copies/mL) at baseline to undetectable (HIV RNA \< 20 copies/mL) at week 12 in the AdhereTech bottle arm versus the routine counseling only arm. |
| TFV-DP Plasma Levels | Baseline and Week 12 | Assess TFV-DP plasma levels to compare to dried blood spot levels |
| Number of Participants Reporting 100% Adherence to Antiretroviral Medications in During to the Prior 4 Days at Week 12. | Week 12 | Analyze participant's self-reported adherence using National Institutes of Health AIDS Clinical Trials Group (ACTG) standardized and validated questionnaire of number of days with no missed doses of medication over prior 4 days (minimum 0, maximum 4). Number of days with missed doses was dichotomized to no missed doses (100% adherence) and ≥ 1 missed dose. |
Participant flow
Recruitment details
Recruitment occurred primarily from the clinic population receiving care for HIV at New York Presbyterian Hospital Center for Special Studies located in New York City. A total of 24 and 42 participants were recruited from the Upper East Side and Chelsea locations respectively from May 2015 to August 2018.
Pre-assignment details
67 were screened for the study and 4 did not enroll because: 1 elected not to participate given excellent adherence to medications, 1 was ineligible after a switch off a tenofovir containing regimen, 1 did not come to the enrollment appointment, and 1 did not provide consent.
Participants by arm
| Arm | Count |
|---|---|
| Routine Counseling + AdhereTech Bottle Participants will receive routine medication adherence counseling and be given the AdhereTech smart bottle with reminders.
Adheretech smart bottle: A smart pill bottle that measures the exact number of pills in the bottle in real-time, sends this HIPAA-compliant data to a central server, and based on the results, can remind participants to take their medication through a phone call or text message.
Routine adherence counseling: Participants will be provided with routine adherence counseling | 30 |
| Routine Counseling Participants will receive routine medication adherence counseling.
Routine adherence counseling: Participants will be provided with routine adherence counseling | 33 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Routine Counseling + AdhereTech Bottle | Routine Counseling | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 49 years | 51 years |
| CD4 | 380 cells/μL | 428 cells/μL | 409 cells/μL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 10 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 20 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 6 Participants |
| HIV RNA <= 20 copies/mL | 16 Participants | 15 Participants | 31 Participants |
| Number of daily antiretroviral pills | 2 pills per day | 3 pills per day | 3 pills per day |
| Number of participants prescribed an Integrase inhibitor containing regimen | 14 Participants | 17 Participants | 31 Participants |
| Number of participants prescribed a NNRTI containing regimen | 6 Participants | 7 Participants | 13 Participants |
| Number of participants prescribed a NRTI containing regimen | 28 Participants | 33 Participants | 61 Participants |
| Number of participants prescribed a Protease inhibitor containing regimen | 10 Participants | 15 Participants | 25 Participants |
| Number of participants prescribed a tenofovir containing regimen | 28 Participants | 33 Participants | 61 Participants |
| Number of participants reporting days of no missed doses in prior 4 days 1 day | 0 Participants | 3 Participants | 3 Participants |
| Number of participants reporting days of no missed doses in prior 4 days 2 days | 4 Participants | 6 Participants | 10 Participants |
| Number of participants reporting days of no missed doses in prior 4 days 3 days | 6 Participants | 2 Participants | 8 Participants |
| Number of participants reporting days of no missed doses in prior 4 days 4 days | 18 Participants | 19 Participants | 37 Participants |
| Number of participants reporting days of no missed doses in prior 4 days No days | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 14 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 11 Participants |
| Race (NIH/OMB) White | 8 Participants | 12 Participants | 20 Participants |
| Sex/Gender, Customized Female | 6 Participants | 8 Participants | 14 Participants |
| Sex/Gender, Customized Male | 23 Participants | 23 Participants | 46 Participants |
| Sex/Gender, Customized Transgender | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 33 |
| other Total, other adverse events | 0 / 30 | 0 / 33 |
| serious Total, serious adverse events | 0 / 30 | 0 / 33 |
Outcome results
Primary
Change in Tenofovir Diphosphate (TFV-DP) Drug Levels
Using dried blood spots from red blood cells, TFV-DP levels will be assessed.
Time frame: Baseline and Week 12
Population: Of the 5 in AdhereTech bottle group missing baseline TFV-DP levels 2 were lost to follow up prior to the visit and 3 are missing levels. 3 participants in AdhereTech group left the study before Week 12. 4 participants in the routine counseling group are missing TFV-DP levels from baseline visit and then 7 left the study prior to Week 12.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Routine Counseling + AdhereTech Bottle | Change in Tenofovir Diphosphate (TFV-DP) Drug Levels | Baseline | 1230 fmol/punch |
| Routine Counseling + AdhereTech Bottle | Change in Tenofovir Diphosphate (TFV-DP) Drug Levels | Week 12 | 1887 fmol/punch |
| Routine Counseling | Change in Tenofovir Diphosphate (TFV-DP) Drug Levels | Baseline | 1108 fmol/punch |
| Routine Counseling | Change in Tenofovir Diphosphate (TFV-DP) Drug Levels | Week 12 | 1084 fmol/punch |
Comparison: The power calculation was based on a null hypothesis of no difference in mean tenofovir-diphosphate (TFV-DP) concentrations between baseline versus week 12. Expected baseline mean (SD): 900 (404) fmol/punch. 12 week mean (SD): 1332 (597) fmol/punch in the AdhereTech bottle arm vs. 900 (404) fmol/punch in control arm. Type 1 error = 0.05, power = 80%, a sample size of 32 per arm (64 total) based on a two-sided t-test with equal variance.p-value: 0.0795% CI: [-0.028, 0.694]t-test, 2 sided
Secondary
Change in Quantitative HIV Viral Load
Comparative changes in quantitative HIV viral load between baseline and Week 12 in the AdhereTech bottle arm versus the routine counseling only arm.
Time frame: Baseline and Week 12
Population: 5 and 7 participants left the AdhereTech bottle and routine counseling groups respectively. And additional participant in the AdhereTech bottle group is missing the Week 12 HIV viral load.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Routine Counseling + AdhereTech Bottle | Change in Quantitative HIV Viral Load | Baseline | 19 copies/mL |
| Routine Counseling + AdhereTech Bottle | Change in Quantitative HIV Viral Load | Week 12 | 19 copies/mL |
| Routine Counseling | Change in Quantitative HIV Viral Load | Baseline | 28 copies/mL |
| Routine Counseling | Change in Quantitative HIV Viral Load | Week 12 | 26 copies/mL |
Comparison: Null hypothesis: Mean HIV viral load is not significantly different in the AdhereTech bottle group compared to the routine counseling only group.p-value: 0.328Kruskal-Wallis
Secondary
Number of Participants Completing the 12 Week AdhereTech Bottle Intervention Compared to the Routine Counseling Only Group.
Feasibility of using the AdhereTech Smart Pill Bottles in individuals living with HIV as measured by the proportion of participants that complete the study compared between arms. A statistically lower proportion in the AdhereTech bottle arm compared to the routine counseling arm would suggest use of the bottle is not feasible.
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Routine Counseling + AdhereTech Bottle | Number of Participants Completing the 12 Week AdhereTech Bottle Intervention Compared to the Routine Counseling Only Group. | 25 Participants |
| Routine Counseling | Number of Participants Completing the 12 Week AdhereTech Bottle Intervention Compared to the Routine Counseling Only Group. | 26 Participants |
Comparison: The null hypothesis is that the proportion of randomized participants that complete a week 12 visit is not lower in the AdhereTech bottle arm.p-value: 0.8995% CI: [-0.179, 0.27]Chi-squared, Corrected
Secondary
Number of Participants Reporting 100% Adherence to Antiretroviral Medications in During to the Prior 4 Days at Week 12.
Analyze participant's self-reported adherence using National Institutes of Health AIDS Clinical Trials Group (ACTG) standardized and validated questionnaire of number of days with no missed doses of medication over prior 4 days (minimum 0, maximum 4). Number of days with missed doses was dichotomized to no missed doses (100% adherence) and ≥ 1 missed dose.
Time frame: Week 12
Population: 5 and 7 participants dropped out between baseline and week 12 in the AdhereTech bottle arm and routine counseling only arms respectively. One participant in the AdhereTech bottle arm did not fully complete the adherence questionnaire at week 12.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Routine Counseling + AdhereTech Bottle | Number of Participants Reporting 100% Adherence to Antiretroviral Medications in During to the Prior 4 Days at Week 12. | 18 Participants |
| Routine Counseling | Number of Participants Reporting 100% Adherence to Antiretroviral Medications in During to the Prior 4 Days at Week 12. | 20 Participants |
Comparison: Null hypothesis: Adherence in the AdhereTech bottle arm is not better than the control arm at Week 12.p-value: 195% CI: [-0.237, 0.276]Chi-squared, Corrected
Secondary
Number of Participants With HIV RNA ≥ 20 Copies/mL at Baseline That Had a Decrease in HIV RNA to < 20 Copies/mL at Week 12 in the AdhereTech Bottle Arm Versus the Routine Counseling Only Arm.
This is a measure of qualitative HIV RNA outcome. The number of participants converting from detectable (HIV RNA ≥ 20 copies/mL) at baseline to undetectable (HIV RNA \< 20 copies/mL) at week 12 in the AdhereTech bottle arm versus the routine counseling only arm.
Time frame: Baseline and Week 12
Population: 5 and 7 participants left the AdhereTech bottle and routine counseling groups respectively. An additional participant in the AdhereTech bottle group is missing the Week 12 HIV viral load.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Routine Counseling + AdhereTech Bottle | Number of Participants With HIV RNA ≥ 20 Copies/mL at Baseline That Had a Decrease in HIV RNA to < 20 Copies/mL at Week 12 in the AdhereTech Bottle Arm Versus the Routine Counseling Only Arm. | 3 Participants |
| Routine Counseling | Number of Participants With HIV RNA ≥ 20 Copies/mL at Baseline That Had a Decrease in HIV RNA to < 20 Copies/mL at Week 12 in the AdhereTech Bottle Arm Versus the Routine Counseling Only Arm. | 7 Participants |
Comparison: Null hypothesis: There is no difference in proportion of participants that go from HIV RNA ≥ 20 copies/mL to HIV RNA \< 20 copies/mL between baseline to Week 12 in the AdhereTech bottle group compared the routine counseling group.p-value: 0.29495% CI: [0.058, 2.044]Fisher Exact
Secondary
TFV-DP Plasma Levels
Assess TFV-DP plasma levels to compare to dried blood spot levels
Time frame: Baseline and Week 12
Population: Funding was not obtained to obtain TFV-DP plasma levels in the study