Measuring and Monitoring Adherence to ART With Pill Ingestible Sensor System

Introduction of antiretroviral therapy (ART) has transformed HIV-infection from a fatal to
manageable disease but adherence to ART remains critical to optimize outcomes. Existing
measures of ART adherence such as self-report, pill counts, electronic pill-bottle caps, and
prescription refills, provide only inferred measures of actual drug intake and most offer no
real-time notification capability. Directly observed therapy measures actual drug intake but
is not practical. These limitations constrain research into medication adherence and more
importantly, limit our ability to develop real-time interventions based on feasible, in vivo
monitoring of adherence among HIV-infected people to facilitate medication-taking. The
Proteus digital health feedback (PDHF) system, a pill ingestible sensor based adherence
measuring and monitoring system developed by Proteus Digital Health, addresses these
limitations. It involves use of an ingestible sensor, a tiny edible material that is
over-encapsulated along with prescribed medication. The sensor is activated by ingestion and
is sensed by a patch worn by the patient with an embedded monitor and sensor. The monitor
sends a Bluetooth signal to a mobile device, which in turn sends an encrypted message to a
central server, thus effecting real-time monitoring that a dose has been taken. The
investigators propose to develop a data receiving hub and add to these components an
automated text message that is sent to the patient when a dose is missed. The ingestible
sensor and patch monitor system is already FDA-approved as safe, but has yet to be tested in
HIV-infected patients in clinical setting. The first goals of this study are to confirm the
bioavailability of over-encapsulated antiretrovirals (ARVs) and to pilot-test the use of the
PDHF system in 15 participants prescribed ARVs to test and identify approaches that optimize
the use of this measuring and monitoring system. The next goals are to determine the system's
feasibility, acceptability, sustainability, accuracy and efficacy in fostering ART adherence.
Feasibility, acceptability and sustainability will be assessed by patients' rating of the
system and the rate of dropping off from using the system. Accuracy will be evaluated by the
associations between adherence to ART measured by the PDHF system and other adherence
measures such as plasma drug level concentrations of ARVs and self-report. Efficacy will be
assessed by comparing adherence of participants assigned to the PDHF system and participants
assigned to usual care (UC) over time, with exploratory outcomes of viral load and CD4. The
investigators will recruit 120 of HIV-infected patients 18 years or older with sub-optimal
adherence. Participants will be randomized to receive the PDHF system or UC for 16 weeks with
monthly assessments. The durability of effects of the PDHF system after stopping the use of
the system will be determined during a 12-week follow-up stage. In summary, The investigators
will evaluate the feasibility, acceptability and sustainability of using the PDHF system;
assess the accuracy of the PDHF system in measuring adherence to ART; and evaluate the
efficacy of the PDHF system for monitoring and leveraging adherence to ART.

Inclusion Criteria:

- HIV-infected individuals in HIV care

- greater than 17 years of age

- demonstrated ability to take over-encapsulated ARVs at time of screening; able to
provide informed consent

- On ART with sub-optimal adherence estimated by either patient (self-reports < 90%
adherence over last 28 days) or treating clinician (e.g., based on gaps in treatment
(e.g., missed appointments) or viral load elevations within last 6 months)

Exclusion Criteria:

- Inability to follow the study procedures manifested during the intake, as evidenced by
mental confusion, disorganization, intoxication, withdrawal, risky or threatening
behavior