Triggered Escalating Real-time Adherence (TERA) Intervention

This 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. They may be
continuing the same ART regimen or starting a new once daily regimen. 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.

TERA is a time-limited (12 weeks) intervention approach that (a) uses wireless electronic
dose monitoring (EDM) to identify dose-times passing with no bottle opening, (b) sends a text
asking about the delay, (c) evaluates response to text and (d) initiates follow-up by an
adherence coach depending on response and if the bottle remains unopened for a designated
period post dosing. Phone based outreach will use problem solving discussion with an
adherence coach, who can use an agreed-upon contact tree to reach the youth through other
individuals. This "boot camp" strategy is used to unsettle or disrupt established
non-adherence behaviors and factors promoting ongoing non-adherence. The TERA intervention
will be compared with standard of care (SOC).

Participants will be followed for 48 weeks, with clinic visits at entry and weeks 4, 12, 24,
36 and 48. Audio computer assisted self-interviews (ACASI) are 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 are also collected at each
study visit.

The primary objective of the study is to compare HIV-virologic suppression (VLS) rates at 12
weeks. Secondary objectives include comparing VLS rates and EDM rates of ART adherence at 24,
36, and 48 weeks as well as patterns of adherence over time.

Inclusion Criteria:

1. Age 13 through 24 years (inclusive)

2. 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

3. Participant aware of his or her HIV infection, as determined by site staff

4. Documented plasma HIV-1 RNA plasma ≥200 copies/mL within 45 days of the date of the
enrollment visit

5. Prescribed antiretroviral therapy for at least 24 weeks or more prior to documented
plasma HIV-1 RNA plasma ≥200 copies/mL.

6. Prescribed a once-daily (one or more pills once a day) ART regimen with at least two
active agents (per clinician judgment or genotype evidence) at enrollment

7. Able to communicate in spoken and written English

8. Currently has a cellular phone that is also able to send and receive text messages

9. Willing and able to provide at least one additional contact phone number (preferably
two) to contact participant

10. 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 institutional review board [IRB] policy, and detailed in each site's protocol
implementation plans [PIPs]) to be screened for and to enroll in this study

Exclusion Criteria:

1. 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

2. Concurrent participation in interventional studies addressing adherence unless
approved in advance by study team

3. Positive pregnancy test at the time of enrollment. If participant becomes pregnant
while on study, they may continue on study

4. Currently using or planning to use an electronic dose monitoring and reminder device
outside of the study