SteadyRx: Smartphone ART Adherence Intervention for Drug Users
Condition: HIV; Medication Adherence
Study type: Interventional

Summary: 
      Antiretroviral therapy (ART) increases life expectancy and quality of life for individuals
      infected with HIV, and can reduce the chance of HIV transmission, but a high degree of
      adherence to ART is required to achieve these benefits. Unfortunately, only 59% of patients
      in North America report ART adherence >90%. Thus, ART adherence interventions are a critical
      part of the fight against HIV/AIDS. Injection drug use and crack cocaine use are major
      factors in the transmission of HIV, and are associated with non-adherence to ART. Several
      types of interventions, most notably directly administered antiretroviral therapy (direct
      observation of antiretroviral administration and patient supports) and contingency management
      (the provision of incentives contingent upon objective evidence of adherence) have been
      effective in promoting ART adherence in drug users. However, a core problem with all ART
      adherence interventions is that their effects do not last after the interventions are
      discontinued. The common finding of post-intervention dissipation of effects suggests that
      ART adherence interventions may need to be long-term or even permanent adjuncts to ART for
      drug users. The investigators intend to develop an intensive intervention that incorporates
      the most effective techniques for promoting ART adherence in drug users, and delivers them in
      a manner that allows for their large-scale implementation as long-term or even permanent
      adjuncts to ART. Thus, we will bundle a targeted group of effective component interventions
      into a smartphone application that is easy for patients to use, simple to manage, and
      maximally convenient for all stakeholders. Our ultimate goal is to produce an intervention
      that is highly effective and scalable. Toward that end, the SteadyRX intervention to be
      developed under this project will be largely automated and will (1) facilitate consultation
      with care providers (2) provide reminders when a dose is overdue, (3) provide electronic
      remote observation of medication-taking, and (4) reward ART adherence. In addition to
      developing this smartphone-based intervention, a pilot study will be conducted in 50 HIV+
      adults with a history of problem drug use. In this study, participants will be randomly
      assigned to receive usual care, or usual care plus the SteadyRX intervention.
    

Detailed description: 
      Antiretroviral therapy (ART) increases life expectancy and quality of life for individuals
      infected with HIV, and can reduce the chance of HIV transmission. These fantastic personal
      and public health benefits require a high level of adherence to the prescribed treatment
      regimen. High rates of virologic suppression can be achieved with an adherence rate of 90%,
      but adherence of 95% or more appears to produce the best combination of a higher probability
      of virologic suppression and a lower probability of the development of resistance to the
      medications. Unfortunately, only 59% of patients in North America report ART adherence >90%.
      Thus, ART adherence interventions are a critical part of the fight against HIV/AIDS, and
      there is a substantial need for novel and effective ART adherence interventions.

      Injection drug use and crack cocaine use are major factors in the transmission of HIV and
      have been associated with non-adherence to ART. Several types of interventions have been
      effective in promoting short-term ART adherence in these populations. Counseling strategies
      and reminders (e.g., beepers, calendars, etc.) have each had modest effects. Still more
      successful approaches have included directly administered antiretroviral therapy (DAART, in
      which patients are observed by care providers as they take their medication), medication
      assisted therapy (e.g., methadone maintenance), and contingency management (monetary
      incentives for maintaining adherence to HIV medications). However, a core problem with all
      ART adherence interventions is that their effects do not appear to last after the
      interventions are discontinued. In a recent review of ART adherence interventions for drug
      users, researchers expressed concern over the "virtual lack of interventions with sustained
      post-intervention adherence and virologic benefits." The common finding of post-intervention
      dissipation of effects suggests that ART adherence interventions may need to be implemented
      as long-term or even permanent adjuncts to ART for drug users.

      The investigators seek to develop an intensive intervention that incorporates the most
      effective techniques for promoting ART adherence in drug users, and deliver them in a manner
      that allows for their large-scale implementation as long-term or even permanent adjuncts to
      ART. The investigators propose a three year development project for an ART adherence
      intervention that bundles a targeted group of effective component interventions into a
      Smartphone application that is easy for patients to use, simple to manage, and maximally
      convenient for all stakeholders. Toward that end, the intervention to be developed under this
      project will (1) facilitate consultation with care providers (2) provide reminders when a
      dose is overdue, (3) provide remote electronic observation of medication-taking, and (4)
      provide incentives for ART adherence. The proposed intervention (SteadyRx) is highly
      innovative: no previous ART adherence intervention has involved direct observation of
      medication administration and contingency management, despite their respective effectiveness
      in isolation. Importantly, no mobile/remote intervention currently under development is as
      intensive as SteadyRx.

      The developmental process for this application will begin with modification of existing
      technology, which will be followed by conducting focus groups with the intended target
      population as well as with physicians, primary care staff, and health administrators,
      respectively, in order to enhance the adoptability of the intervention by including
      application functions and interface design that is sensitive to the needs of all
      stakeholders. Small scale testing with members of the target population will be used to
      further refine the application and produce a beta version for use in a pilot randomized
      controlled trial.

      In the pilot study, 50 HIV+ adults with a history of problem drug use will be randomly
      assigned to receive either usual care services at a primary care facility or these services
      plus the SteadyRx intervention. The project has the following Specific Aims:

        1. Develop the SteadyRx Smartphone intervention

             1. Conduct focus groups with the target population, physicians, primary care staff,
                and health administrators, respectively, prior to creating the application and
                instructional materials

             2. Create alpha versions of the smartphone application and related instructional
                materials

             3. Create a beta version of the application to use in the pilot randomized controlled
                trial.

        2. Implement SteadyRx in a pilot randomized controlled trial

             1. Evaluate SteadyRx's acceptability to stakeholders, user experience, and user
                engagement.

             2. Collect preliminary data on the effectiveness of SteadyRx in improving ART
                adherence, reducing viral load, and promoting high CD4 counts

             3. Collect preliminary assessment of associations between ongoing drug use and health
                literacy and the effectiveness of SteadyRx.

      Overall, the combination of consultation, reminders, direct observation, and incentives for
      adherence, when delivered as a long-term adjunct to ART via Smartphone application could
      prove to be a maximally effective and practical means of realizing the fantastic potential of
      modern ART for improving the lives of individuals with HIV/AIDS and for reducing the rate of
      HIV transmission by high-risk patients.

      STUDY PROCEDURES Application Development Alpha Version. As the first step in the development
      of the application, the investigators will create an alpha version of the application that
      includes the PillWatch feature. Note that the PillWatch feature will require only minor
      modification from the existing Mōtiv8 technology used by Dallery (Co-I). Other aspects of the
      planned application will require more substantial development and thus will not be fully
      developed until after the focus group sessions described below.

      Focus Groups. As the second step in the development of the application, the investigators
      will conduct three focus group sessions. All focus groups will be designed and moderated by
      Baltimore Research, a full service marketing research company with over 50 years of
      experience (See Facilities and Other Resources for further details). Baltimore Research will
      also handle all data collection and analysis for the focus group sessions and provide the
      study team with a final report for each session. Each focus group will include a relatively
      homogeneous set of stakeholders: Physicians/primary care staff, health administrators (e.g.,
      see Priority Partners letter of support), and patients, respectively. All focus groups will
      include approximately eight participants, as this has been identified as an ideal number of
      participants in a focus group session. In order to ensure that approximately eight
      participants will be included, the investigators will attempt to recruit at least 10
      participants, because all participants must show up at the same time for a specific scheduled
      session, and this usually results in some people who agree to participate but do not show up
      at the scheduled time. These groups will be held as one-time sessions designed to generate
      ideas that will enhance the application's usability and adoptability from the perspective of
      the professionals who are most likely to be involved in the institutional decision making
      processes relevant to the dissemination of the proposed intervention. The investigators
      anticipate that recruitment of health professionals will be straightforward given our
      extensive connections to professionals throughout the local health care systems in Baltimore,
      and consultation by Baltimore Research will ensure that these recruitment processes are free
      of bias. The third focus group session (patients) will be the beginning of an iterative
      process in which the investigators first solicit ideas about the functionality and interface
      of the application. Participants for this focus group will be recruited using methods
      identical to those described below for the pilot randomized controlled trial.

      Create the Beta Version. Following the initial four focus group sessions, the beta version of
      the application will be created with the critical features described above. The end product
      of this part of the development process will be the beta version that will be used in the
      pilot study described below.

      PILOT STUDY The investigators expect that all participants will be patients at the
      Comprehensive Care Practice (CCP). CCP is located in the Mason F. Lord Building at the Johns
      Hopkins Bayview Medical Center in Baltimore, MD. CCP provides primary medical care to ~450
      HIV+ adults and will serve as the recruitment site.

      Participants will be recruited from their regularly scheduled HIV care appointments at the
      CCP at which current viral load and CD4 counts are evaluated. Any HIV+ patient with a
      substance use disorder will be told by their CCP doctor about our research study and given a
      recruitment flyer that explains the benefits of participation. If they express interest, the
      doctor will immediately contact the CCP Medical Case Manager who is in charge of study
      recruitment and assessment (hereafter, outreach coordinator). The outreach coordinator will
      briefly explain the intake interview process and basic purpose of the study. If the patient
      agrees to move forward they will begin with a formal consent process. During this process,
      the outreach coordinator will read the consent form aloud in its entirety while the
      participant follows along. After signing the consent form, the patient will proceed
      immediately to the intake interview unless their schedule precludes it, in which case they
      will provide contact information and schedule the intake interview for a time on the next day
      or as soon as possible. Participants who have signed consent but who have not returned to CCP
      will be given reminder calls related to their scheduled intake interview. They will also
      receive follow up calls if they fail to show up for their scheduled appointment time.

      For any given pilot study participant, study participation will last for six months, and will
      include an intake visit plus six visits at 30 day intervals thereafter. For focus group
      participants, study participation will consist of a single focus group session.
    

Intervention name(s): SteadyRx
Intervention type(s): Behavioral
Intervention description(s): The proposed intervention consists of four core elements. The intervention will include a Smartphone application that allows direct interaction with the SteadyRx system, as well as automatic events controlled via a central server. The CONSULT element will facilitate patient-provider communication with links to care providers and other care resources. The REMIND element will provide telephonic reminders for late doses. The OBSERVE element will feature electronically observed dosing through time-stamped video recordings made on the Smartphone and sent securely to a central server. The REWARD element will feature monetary incentives designed to reinforce short- and long-term medication adherence and promote reductions in viral load.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Incentives; Smartphone; Mobile intervention; eDOT; Adherence reinforcement; Drug users