TERA (Triggered Escalating Real-time Adherence)
The TERA project is a phase II, two-arm, randomized, open-label study. Eligible participants will have failed ART therapy, defined as having detectable HIV virus (HIV-1 RNA ≥200 copies/ml) within 45 days of enrollment despite having been on ART for at least 24 weeks. Participants will be 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. Institutional balancing will ensure roughly equal numbers of participants in each study arm at each site. After being randomized to study arm, a second procedure will randomly select a subset of participants to engage in the qualitative interviews. To promote ART adherence, participants in the TERA intervention arm will receive intensive, time-limited (12-weeks) adherence coaching, where trained counselors work with participants through video enabled conferencing at three care visits and interact with text, phone, and video as-needed in real-time for any missed doses signaled by the participant’s electronic dose monitoring (EDM) device. This intensive “boot camp” strategy is used to unsettle or disrupt established non-adherence behaviors and factors promoting ongoing non-adherence but for a time-limited period. Counselors are remotely located and interact with the local study team on a case by case basis. All participants use EDM throughout their 48 weeks of participation as a method to track adherence. The main goal of the TERA intervention is to promote viral suppression by the 3-month mark, with additional objectives including sustained viral suppression throughout the 48-weeks of participation.
TERA Intervention Manual for Monitors and Coaches
B) Intervention and Data Collection Overview.
The study will last approximately 96 weeks total. Participants will be followed for 48 weeks.
120 youth living with HIV (YLWH)
Potential participants must meet all of the following criteria in order to be included in this study:
Age 13 through 24 years (inclusive)
Confirmation of HIV-1 Infection as documented in the participant’s medical record by at least two of the following criteria:
Reactive HIV screening test result with an HIV antibody or HIV antibody/antigen-based, Food and Drug Administration (FDA)-licensed assay followed by a positive supplemental assay (e.g., HIV-1 Western Blot, HIV-1 indirect immunofluorescence, HIV-1/HIV-2 discriminatory immunoassay);
Plasma HIV-1 quantitative ribonucleic acid (RNA) assay >1,000 copies/mL;
Positive HIV-1 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assay; or
Positive plasma HIV-1 RNA qualitative assay
Participant aware of his or her HIV infection, as determined by site staff
Documented HIV-1 RNA plasma ≥200 copies/mL within 45 days of the date of the enrollment visit
Prescribed first-line antiretroviral therapy at least 24 weeks or more prior to documented plasma HIV-1 RNA plasma ≥200 copies/mL. Note: Any prior switch of antiretrovirals, defined as a change of a single drug or multiple drugs simultaneously from what the patient was first started on, for tolerability/safety, access to medications, or convenience/simplification, and NOT for treatment failure (HIV Viral Load > 200 copies/mL despite 24 or more weeks of being prescribed antiretroviral therapy) is still considered as first-line therapy.
Continuing or restarting their first-line antiretroviral therapy (as defined above) OR planned to be switched to a second line ART regimen with at least two active agents (per clinician judgment or genotype evidence) at enrollment
Able to communicate in spoken and written English
Currently has a cellular phone that is also able to send and receive text messages
Willing and able to provide at least one additional contact phone number (preferably two) to contact participant
Able and willing to provide written informed assent/consent and able to obtain written parental or guardian permission (if required as specified by the site, by state law, and/or IRB policy, and detailed in site SSPs) to be screened for and to enroll in this study
To be considered eligible for enrollment, an individual must not meet any of the criteria listed below.
Gross cognitive limitations, acute emotional instability, or medical or mental health illness that in the opinion of site personnel would impair the individual’s ability to provide informed consent and/or interfere with the protocol’s objectives.
Concurrent participation in interventional studies addressing adherence unless approved in advance by study team
Positive pregnancy test at the time of enrollment. If participant becomes pregnant while on study, they may continue on study
Currently using or planning to use an electronic dose monitoring and reminder device outside of the study
Primary Outcome Measure:
1. Proportion 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.
2. Proportion 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.
Secondary Outcome Measure:
3. Proportion 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 with no HIV-1 RNA measurement within the week window are classified as failures.
4. Proportion 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 with no HIV-1 RNA measurement within the week window are classified as failures.
5. Proportion 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.
6. Percent of days with all doses taken per week from weeks 0-12, 12-24, 24-36 and 36-48
For each participant, the percentage of days in each 7-day period in which all doses were taken is calculated, and then averaged across the 12-week interval (or number of weeks with available data).
7. Percent of days with all doses taken within defined acceptable windows (within 4 hours for once/day ART and within 2 hours for twice/day ART) per week from weeks 0-12, 12-24, 24-36 and 36-48
For each participant, the percentage of days in each 7-day period in which all doses were taken within the defined acceptable windows (within 4 hours for once/day ART and within 2 hours for twice/day ART) is calculated, and then averaged across the 12 week interval (or number of weeks with available data).
8. Incidence rate (per 100 days) of gaps between dosing of at least 7 consecutive days between 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 gaps between doses of >7 consecutive days relative to the number of days with data reported, times 100. Consecutive gaps of more than 7 days increase the gap count by one, e.g. missing 20 days counts as 2 gaps.