An interventional study of TERA Intervention (TERA) and Standard of Care (SOC) in HIV Infections, sponsored by University of North Carolina, Chapel Hill. Completed at 8 sites in United States. Open to participants aged 13 Years to 24 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-03-11.
Sponsored by University of North Carolina, Chapel Hill · Not applicable, Interventional, and Supportive care
Youth Living with HIV (YLWH) often face unique challenges achieving high and sustained rates of adherence to their antiretroviral therapy (ART). Poor adherence can lead to unsuppressed virus, more advanced HIV disease and poorer health outcomes, eventually exhausting treatment options. To date however, there are few demonstrated interventions for youth failing first line therapy. This study evaluated a novel intervention that used remote coaching through video enabled counseling sessions, an Electronic Dose Monitoring (EDM) pill bottle that notified an adherence coach when youth failed to open/close the device around dose time, and problem solving outreach by the coach in response to not dosing from the EDM. This intensive 'boot camp' strategy was implemented for 12 weeks followed by observation through 48 weeks.
This was a Phase II, two-arm, randomized, open-label study. Eligible participants had failed ART therapy, defined as having a detectable plasma Human Immunodeficiency Virus - Type 1 Ribonucleic Acid (HIV-1 RNA) ≥200 copies/ml within 45 days of enrollment despite having been prescribed ART for at least 24 weeks. They could continue the same ART regimen or start a new once daily regimen. Participants were stratified by age (\<18 vs. ≥18 years of age) and randomized in equal proportions to receive the study intervention (TERA) or standard of care (SOC), with no enrollment limits in each stratum. Target accrual was 120 participants to be enrolled over one year.
TERA was a time-limited (12 weeks) intervention approach that (a) used wireless electronic dose monitoring (EDM) to identify dose-times passing with no bottle opening, (b) sent a text asking about the delay, (c) evaluated response to the text and (d) initiated follow-up by an adherence coach depending on the response and if the bottle remained unopened for a designated period post dosing. Phone based outreach used problem solving discussion with an adherence coach, who could use an agreed-upon contact tree to reach the youth through other individuals. This "boot camp" strategy was used to unsettle or disrupt established non-adherence behaviors and factors promoting ongoing non-adherence.
Participants were followed for 48 weeks, with clinic visits at entry and weeks 4, 12, 24, 36 and 48. Audio computer assisted self-interviews (ACASI) were conducted every 12 weeks to collect information on adherence, motivation and skills, social support, mental and physical health functioning. Viral loads, medication and medical histories were also collected at each study visit.
The primary objective of the study was to compare HIV-virologic suppression (VLS) rates at 12 weeks. Secondary objectives included comparing VLS rates and EDM rates of ART adherence at 24, 36, and 48 weeks as well as patterns of adherence over time.
Major changes after the start of enrollment:
At the time of the study pause, data collection for the Primary Outcome Measures was complete, so the analyses proposed in the original Statistical Analysis Plan were not affected. Follow-up for the Secondary Outcome Measures involving HIV-1 RNA measurements and adherence was incomplete, with 33% of participants still on study. Because of the possibility that participant behavior and adherence to ART would differ pre- and post-pandemic, and it would not be possible to collect HIV-1 RNA measurements within the required visit windows (sites were actively trying to keep patients from coming into care unless urgently needed), the Study Team decided to base analyses on data collected prior to the COVID-19 study pause. In addition, because the secondary virologic outcome measures were a combination of HIV-1 RNA levels and data completeness (classifying participants with no HIV-1 RNA measurement within the allowed visit window as "virologic failures"), the analysis population for these outcome measures only included participants with sufficient time on study to reach each study visit.
These changes were implemented on June 2, 2020 in a Letter of Amendment (LOA) to TERA Protocol Version 3.1. The LOA detailed three modifications due to COVID-19 study visit suspension, but did not affect the existing protocol:
On September 24, 2020, the Study Team released a memo to the sites extending the date for the Week 48 study visit to October 12, 2020.
Results for secondary outcome measures 3 to 8 are based on the pre COVID-19 study pause database as of March 20, 2020.
Results for secondary outcome measures 9 and 10 are based on the complete study database as of October 12, 2020.
4,734 studies on the registry are indexed under HIV Infections; 244 are open to participants now.
This study's enrollment of 89 is above the median of 80 across 3,489 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →University of North Carolina, Chapel Hill is the lead sponsor of 1,372 studies on the registry; 133 are open to participants now.
Of its 161 completed or terminated interventional studies of FDA-regulated products, 139 (86%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Confirmation of -1 Infection as documented in the participant's medical record by at least two of the following criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Standard of Care for adherence support at Site
Behavioral: Standard of Care (SOC)
Triggered, escalating, real-time adherence (TERA) intervention for 12 weeks.
Behavioral: TERA Intervention (TERA)
A sequence of adherence support strategies implemented at care visits and as needed on the basis of EDM data. Components include: (1) remote education/preparation with an adherence coach conducted with VSee software (video conferencing) at site at baseline, week 4 and week 12; (2) one-way text alert at dose time when bottle has not yet been opened for that dosing window (users can disable this on request); (3) missed dose two-way outreach text asking "What's the plan?" which gets sent to both the participant's phone and a study phone; and (4) implementation of the coach-outreach (phone, text, remote counseling) triggered by missed doses or as a check-in to inquire about the well-being of the youth (once per week when no other contact with coach occurred the week prior).
Cell-phone reminders, patient-education, adherence planning (medication management), and checking-in on adherence at clinical care visits, as well as Viral load (VL) monitoring with patient feedback on VL, are used at sites. Less common, but available as a general service at some sites, on several websites, and at many pharmacies, youth may also receive text messages at dose times, for appointment reminders, and for refill reminders.
Percentage of Participants With Plasma Human Immunodeficiency Virus - Type I Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/mL at Week 12
Participants with HIV-1 RNA \< 50 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA \>= 50 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.
Time frame: 12 weeks post enrollment
Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 12
Participants with HIV-1 RNA \< 200 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA \>= 200 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.
Time frame: 12 weeks post enrollment
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24, 36 and 48
Participants with HIV-1 RNA \< 50 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA \>= 50 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.
Time frame: 24, 36 and 48 weeks post enrollment
Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Weeks 24, 36 and 48
Participants with HIV-1 RNA \< 200 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA \>= 200 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.
Time frame: 24, 36 and 48 weeks post enrollment
Percentage of Participants With HIV-1 RNA < 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks
Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are \< 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is \< 200 copies/mL. Otherwise, the participant is classified as a failure.
Time frame: 48 weeks post enrollment
Percentage of Days With Dose Taken From Weeks 0-12, >12-24, >24-36 and >36-48
For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken divided by the number of days with data reported in the Electronic Monitoring Device (EDM).
Time frame: Enrollment through 48 weeks
Percentage of Days With Dose Taken Within Defined Acceptable Window (+/- 4 Hours) From Weeks 0-12, >12-24, >24-36 and >36-48
For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken within acceptable window divided by the number of days with data reported in the EDM.
Time frame: Enrollment through 48 weeks
Incidence Rate of 7-day Gaps Between Dosing for Weeks 0-12, >12-24, >24-36 and >36-48
For each participant, the incidence rate during each 12 week interval is calculated as the ratio of the number of 7-day gaps between doses relative to the number of weeks with data reported, times 12. Consecutive gaps of more than 7 days increase the gap count by one, e.g., missing 20 days counts as 2 gaps.
Time frame: Enrollment through 48 weeks
Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 48
Participants with HIV-1 RNA \< 200 copies/mL at Week 48 are classified as successes. Participants with HIV-1 RNA \>= 200 copies/mL or with no HIV-1 RNA measurement after 44 weeks follow-up are classified as failures.
Time frame: 48 weeks post enrollment
Percentage of Participants With HIV-1 RNA < 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks
Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are \< 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is \< 200 copies/mL. Otherwise, the participant is classified as a failure.
Time frame: 12, 24, 36, and 48 weeks post enrollment
Participants were enrolled at 10 sites in the United States between April 12, 2018 and September 30, 2019.
| Milestone | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Started | 46 | 43 |
| Started study intervention | 45 | 43 |
| Completed | 31 | 32 |
| Not completed | 15 | 11 |
| Withdrew: Lost to follow-up | 11 | 8 |
| Withdrew: Death | 2 | 1 |
| Withdrew: Withdrawal by subject | 1 | 2 |
| Withdrew: Site closed before any data collected | 1 | 0 |
Participants with HIV-1 RNA \< 50 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA \>= 50 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.
| Percentage of participants | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Percentage of Participants With Plasma Human Immunodeficiency Virus - Type I Ribonucleic Acid (HIV-1 RNA) Levels Less Than (<) 50 Copies/mL at Week 12 | 24.4 | 20.9 |
Participants with HIV-1 RNA \< 200 copies/mL within the week 12 window (+/- 14 days) are classified as successes. Participants with HIV-1 RNA \>= 200 copies/mL or with no HIV-1 RNA measurement within the week 12 window are classified as failures.
| Percentage of participants | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 12 | 35.6 | 34.9 |
Participants with HIV-1 RNA \< 50 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA \>= 50 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.
| Percentage of participants | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Week 24 | 36.4 | 23.3 |
| Week 36 | 15.6 | 19.4 |
| Week 48 | 24.0 | 27.6 |
Participants with HIV-1 RNA \< 200 copies/mL within each week window (+/- 28 days) are classified as successes. Participants with HIV-1 RNA \>= 200 copies/mL or who had the opportunity to reach the study visit week and with no HIV-1 RNA measurement within the week window are classified as failures.
| Percentage of participants | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Week 24 | 40.9 | 27.9 |
| Week 36 | 21.9 | 33.3 |
| Week 48 | 32.0 | 27.6 |
Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are \< 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is \< 200 copies/mL. Otherwise, the participant is classified as a failure.
| Percentage of participants | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks | 8.0 | 13.8 |
For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken divided by the number of days with data reported in the Electronic Monitoring Device (EDM).
| Percentage of days with dose taken | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Weeks 0 - 12 | 41.0 (20.5 to 59.0) | 72.1 (46.5 to 89.2) |
| Weeks >12 - 24 | 14.3 (1.2 to 32.1) | 40.5 (10.7 to 70.2) |
| Weeks >24 - 36 | 2.4 (0.0 to 14.3) | 17.2 (2.3 to 40.5) |
| Weeks >36 - 48 | 1.2 (0.0 to 7.4) | 1.2 (0.0 to 30.0) |
For each participant and each 12-week period, the percentage is calculated as the number of days with dose taken within acceptable window divided by the number of days with data reported in the EDM.
| Percentage of days dose taken on time | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Weeks 0 - 12 | 21.4 (8.4 to 38.6) | 62.7 (30.1 to 84.3) |
| Weeks >12 - 24 | 7.1 (0.0 to 16.7) | 27.4 (7.1 to 57.1) |
| Weeks >24 - 36 | 2.4 (0.0 to 9.5) | 10.7 (0.0 to 35.7) |
| Weeks >36 - 48 | 0.0 (0.0 to 4.8) | 1.2 (0.0 to 22.5) |
For each participant, the incidence rate during each 12 week interval is calculated as the ratio of the number of 7-day gaps between doses relative to the number of weeks with data reported, times 12. Consecutive gaps of more than 7 days increase the gap count by one, e.g., missing 20 days counts as 2 gaps.
| Ratio | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Weeks 0 - 12 | 4.17 (3.61 to 4.82) | 1.66 (1.31 to 2.11) |
| Weeks >12 - 24 | 6.91 (6.16 to 7.75) | 4.43 (3.81 to 5.15) |
| Weeks >24 - 36 | 8.19 (7.28 to 9.21) | 6.65 (5.84 to 7.57) |
| Weeks >36 - 48 | 9.54 (8.37 to 10.89) | 8.81 (7.76 to 10.00) |
Participants with HIV-1 RNA \< 200 copies/mL at Week 48 are classified as successes. Participants with HIV-1 RNA \>= 200 copies/mL or with no HIV-1 RNA measurement after 44 weeks follow-up are classified as failures.
| Percentage of participants | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 200 Copies/mL at Week 48 | 23.3 | 25.6 |
Participants are classified as successes if both the week 12 (+/- 14 days) and week 48 (+/- 28 days) HIV-1 RNA measurements are \< 200 copies/mL and at least one of the week 24 (+/- 28 days) or week 36 (+/- 28 days) HIV-1 RNA measurements is \< 200 copies/mL. Otherwise, the participant is classified as a failure.
| Percentage of participants | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 200 Copies/mL at 12 Weeks and Maintained Through 48 Weeks | 7.0 | 11.6 |
Collected over From study entry to study completion (approximately 48 weeks). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Standard of Care (SOC) | 2/45 (4.4%) | 3/45 (6.7%) | 0/45 (0%) |
| TERA Intervention (TERA) | 1/43 (2.3%) | 4/43 (9.3%) | 2/43 (4.7%) |
| Event | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Axillary abscessInfections and infestations | 0/45 | 1/43 |
| Pneumothorax acute recurrent with shortness of breath, hypoxia and hypokalemiaRespiratory, thoracic and mediastinal disorders | 0/45 | 1/43 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 0/45 | 1/43 |
| HSV proctitisInfections and infestations | 0/45 | 1/43 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 0/45 | 1/43 |
| Facial cellulitis and MRSA positive wound of the tragusInfections and infestations | 0/45 | 1/43 |
| AIDSInfections and infestations | 0/45 | 1/43 |
| Cardiac eventCardiac disorders | 1/45 | 0/43 |
| Esophageal candidiasis and pelvic inflammatory diseaseInfections and infestations | 1/45 | 0/43 |
| Gunshot wound to headInjury, poisoning and procedural complications | 1/45 | 0/43 |
| Event | Standard of Care (SOC) | TERA Intervention (TERA) |
|---|---|---|
| Suicidal ideationPsychiatric disorders | 0/45 | 2/43 |
Includes participants who started study intervention
| Age, Continuous(years) | Standard of Care (SOC) | TERA Intervention (TERA) | Total |
|---|---|---|---|
| Median | 22.1 (16.5 to 24.8) | 22.3 (13.7 to 24.8) | 22.2 (13.7 to 24.8) |
| Age, Customized(Participants) | Standard of Care (SOC) | TERA Intervention (TERA) | Total |
|---|---|---|---|
| 13 - 17 years | 5 | 4 | 9 |
| 18 - 21 years | 16 | 13 | 29 |
| 22 - 25 years | 24 | 26 | 50 |
| Sex: Female, Male(Participants) | Standard of Care (SOC) | TERA Intervention (TERA) | Total |
|---|---|---|---|
| Female | 19 | 21 | 40 |
| Male | 26 | 22 | 48 |
| Ethnicity (NIH/OMB)(Participants) | Standard of Care (SOC) | TERA Intervention (TERA) | Total |
|---|---|---|---|
| Hispanic or Latino | 4 | 5 | 9 |
| Not Hispanic or Latino | 41 | 34 | 75 |
| Unknown or Not Reported | 0 | 4 | 4 |
| Race (NIH/OMB)(Participants) | Standard of Care (SOC) | TERA Intervention (TERA) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 40 | 34 | 74 |
| White | 2 | 0 | 2 |
| More than one race | 1 | 2 | 3 |
| Unknown or Not Reported | 2 | 6 | 8 |
| Region of Enrollment(Participants) | Standard of Care (SOC) | TERA Intervention (TERA) | Total |
|---|---|---|---|
| United States | 45 | 43 | 88 |
| Mode of transmission(Participants) | Standard of Care (SOC) | TERA Intervention (TERA) | Total |
|---|---|---|---|
| Horizontal transmission | 24 | 25 | 49 |
| Vertical transmission | 21 | 18 | 39 |
| Plasma Human Immunodeficiency Virus - Type 1 Ribonucleic Acid (HIV-1 RNA)(Participants) | Standard of Care (SOC) | TERA Intervention (TERA) | Total |
|---|---|---|---|
| 200 - <400 copies/mL | 4 | 6 | 10 |
| 400 - <10,000 copies/mL | 25 | 21 | 46 |
| 10,000 - <50,000 copies/mL | 9 | 5 | 14 |
| >= 50,000 copies/mL | 7 | 11 | 18 |
1 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
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University of North Carolina, Chapel Hill →