Supporting Sustained HIV Treatment Adherence After Initiation

HIV Infections Clinical Trial

— SUSTAIN  

Official title:

Supporting Sustained HIV Treatment Adherence After Initiation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05040841
• Other study ID #: H-41920
• Secondary ID: 1R01MH125703-01A
• Status: Recruiting
• Phase: N/A
• Start date: March 9, 2022
• Est. completion date: June 2026

Study information

• Verified date: June 2023
• Source: Boston University
• Contact: Lora Sabin, PhD MA
• Phone: +16179218864
• Email: lsabin[@]bu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will implement a 24-month fractional factorial design study (Aim 1). The investigators will recruit 510 patients initiating antiretroviral therapy (ART) at three City of Cape Town ART clinics. Each patient will have adherence monitored using the Wisepill® electronic adherence monitoring device (EAM). After eligibility has been confirmed, each participant will be randomized to one of 16 experimental conditions. Each condition includes a unique combination of five adherence intervention components. Three of these components focus on identifying individuals with poor adherence, with increasing degrees of sophistication, with immediate linkage to adherence support. Two components focus on supporting good adherence. They both supplement the existing adherence support program delivered at the study clinics operated by City of Cape Town (standard of care component). Based on Self-Determination Theory, the investigators postulate these intervention components will: 1) enhance feelings of autonomy support, social support, and knowledge; 2) improve motivation and self-competence; and 3) increase ART retention, adherence, and viral suppression. A subset of the participants, as well as clinic staff, will be invited to in-depth interviews to explore mediating factors (Aim 1) and the implementation process (Aim 2); and the data collected in Aims 1 and 2 will be used to explore cost effectiveness (Aim 3).

Description:

The study's primary research goal is to identify the optimal combination of evidence-based and scalable HIV interventions for low-resource, high-burden settings. The investigators propose to 1) test the relative contribution of five promising intervention components; 2) collect cost and other implementation data; and 3) create a multi-component intervention package to optimize cost-effectiveness and implementation success. Of the five components, three are methods of non-adherence detection plus patient outreach; two are adherence support methods that can be integrated into Cape Town healthcare systems. These will not overcome all challenges that ART patients experience (e.g., structural barriers such as food insecurity) but they represent scalable, feasible, acceptable, and effective options. Notably, they are all behavioral approaches grounded in the experience and priorities of local health officials with whom the investigators have worked to identify scaleable interventions. While the study will be in Cape Town, it is broadly adaptable to other resource-limited settings. The gold standard for testing interventions is the randomized controlled trial (RCT), which minimizes bias when testing cause and effect of a new exposure. When testing an intervention with more than one element, however, untangling the effect of individual elements is impossible. Indeed, data on the performance of individual components and their interactions-critical for developing and refining the components of a packaged intervention-is lost in an RCT. Notably, clinical care typically relies on packages of services, not single interventions, and packaged interventions are recommended for ART support. An effective way to test a multi-component intervention is to use the novel Multiphase Optimization STrategy (MOST), an engineering-inspired method for identifying the most efficacious combination of components in a packaged intervention, thus allowing researchers to drop inactive or weakly-performing components and construct an optimized package based on effect, cost, and other features. Once the optimized multi-component intervention is chosen, an RCT or quasi-experiment can follow to determine whether the optimized package yields superior outcomes compared to existing standards. MOST encompasses three phases: 1) preparation; 2) optimization; and 3) evaluation, often in an RCT. In this project, we have completed preparation, including a pilot study in Cape Town. SUSTAIN will comprise the middle optimization phase. The evaluation phase will be the focus of a future study. The specific aims are: Aim 1. Employ a highly efficient fractional factorial design to determine the effects of five intervention components on the primary outcome (HIV viral suppression) and secondary outcomes (ART adherence measured by EAM, ART retention per clinic records, days of unsuppressed virus, time to nonadherence detection, and time to linkage to support). The investigators will explore effect mechanisms quantitatively and qualitatively. Aim 2. Evaluate the intervention components to address implementation, service, and client outcomes according to the Proctor framework. Data collection will involve tracking of intervention component use, time and motion studies, and quantitative surveys and qualitative interviews with participants and staff. Aim 3. Use the effectiveness data collected in Aim 1 and the implementation and client outcomes in Aim 2 to model the multi-component intervention optimized for cost-effectiveness and implementation success. Study Summary This study is designed to advance the translation of evidence-based interventions into clinical settings to benefit patients. There is ample evidence on what works to support ART adherence and retention-much of it from our own research. The investigators partnered with local officials and clinical staff in Cape Town to review the evidence and to conduct formative research to identify the most effective, acceptable, and feasible intervention options for patients and providers. The proposed study represents the next critical step: the investigators will test the intervention components that emerged from the formative work, encompassing elements to both rapidly identify nonadherent patients and to strengthen the support they receive once identified, to provide the data needed to construct the most cost-effective and sustainable multi-component intervention. The choice of intervention components will allow a critical test of advanced monitoring technology compared to simpler tools to identify nonadherence. By using an innovative MOST design to guide collection and analysis of efficacy, cost, and other implementation data, the study aligns with NIH's goals of using novel scientific methods to advance implementation science.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 510
• Est. completion date: June 2026
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria - Main study:

• Adults (=18 years) and adolescents 16-17 years.
• HIV-positive and attending a local City of Cape Town (COCT) clinic to commence ART.
• Able to provide full informed consent, with a written signature. For those who are illiterate, a witness will be present throughout the process and will sign the form, while the participant will add their right thumb print. For those who are aged 16-17 years, informed written assent will be obtained, and the adolescent must have a parent or guardian who can provide full informed consent (see **below for how parent/guardian is defined for this purpose).
• Access to a working cellphone and willingness to receive study-related messaging on that phone.
• Willingness to comply with study procedures, including providing regular updates of contact details /locator information, and use a EAM device for the duration of participation. Other Inclusion Criteria: Aim 1: In-depth interviews (IDIs) with subset of trial subjects at baseline and months 12 and 24.
• Participation in the main trial.
• Self-reported prior experience with substance use, depression, gender inequity, stigma, or transport/clinic issues. Aim 2: Questionnaires and IDIs with staff members at study clinics (three total clinics).
• Adults (=18 years)
• Staff at study clinics, providing HIV care and/or treatment. Aim 2: Focus group discussion (FGD) with City of Cape Town officials.
• Adults (=18 years)
• Staff at City of Cape Town.

Exclusion Criteria - Main study:

• Clinical conditions as assessed by the COCT clinic clinicians at first visit e.g. renal disease, which preclude the use of a single tablet regimen (with the exception of those on tuberculosis (TB) treatment who are required to take an extra dose of dolutegravir daily).
• Planning to leave Cape Town permanently within the next 24 months.
• Being perinatally infected with HIV. Being infected from birth typically means a set of experiences and complications at a young age that require unique and special attention.
• If an adolescent, taking their ART medication as a syrup, as they are required to use the electronic adherence monitor (Wisepill device), which is only suitable for tablets. Other Inclusion Criteria: Aim 1: IDIs with trial subjects.
• None. Aim 2: Questionnaires and IDIs with staff members at clinics. • None. Aim 2: FGD with City of Cape Town officials.
• None.

Related Conditions & MeSH terms

• Adherence, Medication
• HIV Infections

Intervention

Behavioral:
• M1/OTR: Immediate outreach to subject due to unsuppressed viral load test result
Standard of care viral loads are drawn at month 4, month 12 and annually thereafter. Those with a raised viral load are often not immediately recalled, but identified at their next visit (1-2 months later) and asked to attend the "Risk of Treatment Failure" (ROTF) clinic for adherence support when they next attend. For subjects assigned to M1 we will add a call or other outreach (e.g., text, Whatsapp, in accordance with the outreach methods subjects indicate are appropriate for them at the Enrollment visit); to the subject as soon as a raised viral load result is received (±3-5 days), thus expediting entry to existing adherence support. There are two chances to be identified as nonadherent and linked immediately to existing adherence support in the first 12 months of care with M1.
• M2/PRM: Immediate outreach to subject after a missed pharmacy refill
The subject will be contacted if he/she fails to collect medication from the pharmacy. A subject who is =7 days late for a monthly medication pick-up or 14 days late for a 2-monthly pick-up will be notified, again expediting entry to existing adherence support. There are 8-10 chances of being identified as nonadherent and linked immediately to existing adherence support in the first 12 months of care with M2.
• M3/EAM: Immediate outreach to subject after EAM-identified missed doses
The subject will be contacted if he/she misses =4 doses or any three consecutive doses in a 14-day period, reviewed weekly, as identified by the EAM (electronic adherence monitor). There are 52 chances of being identified as nonadherent and linked immediately to existing adherence support in the first 12 months of care with M2.
• S1/Text: Weekly check-in texts
Subject will receive weekly check-in texts in addition to the core adherence support component in the event they are identified as nonadherent and are linked with the Risk of Treatment Failure clinics. Subjects will be sent weekly simple but supportive text messages e.g. "how are you?" with the offer of a follow-up voice call for 16 consecutive weeks after being identified as nonadherent.
• S2/Peer: Enhanced peer group support
Subject will receive an enhanced form of peer group support. Standard of care Basic peer groups are led by lay counsellors and provide social support and education; this will continue to be provided to all patients who are not assigned to the enhanced version. "Enhanced" peer group support will replace the Basic standard of care 4 x 60 minute peer groups; and aim to improve long-term maintenance of adherence through motivational interviewing over 4-8 weeks.

Locations

Country	Name	City	State
South Africa	Mzamomhle	Cape Town	Western Cape
South Africa	Phumlani	Cape Town	Western Cape
South Africa	Weltevreden Valley	Cape Town	Western Cape

Sponsors (5)

Lead Sponsor	Collaborator
Boston University	Desmond Tutu HIV Foundation, Massachusetts General Hospital, National Institute of Mental Health (NIMH), New York University

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HIV viral suppression at 24 months	This outcome will measure the effect of the interventions on HIV viral suppression from enrollment to the end of study participation. HIV viral suppression will be defined as % plasma viral load (VL) <50 copies/mL (dichotomous).	24 months
Secondary	HIV viral suppression at 12 months	This outcome will be an intermediary outcome measure performed half-way through study participation. HIV viral suppression will be defined as % plasma VL <50 copies/mL (dichotomous).	12 months
Secondary	Change in HIV viral load between baseline and 12 months	This will measure the effect on HIV viral load of exposure to interventions during the first half of study participation. It will be measured as the change in HIV viral load, defined as the mean change in HIV plasma between month 0 and month 12 post-enrollment (continuous).	baseline, 12 months
Secondary	Change in HIV viral load between baseline and 24 months	This will measure the effect on HIV viral load of exposure to interventions over the entire course of study participation. It will be measured as the change in HIV viral load, defined as the mean change in HIV plasma between month 0 and month 24 post-enrollment (continuous).	baseline, 24 months
Secondary	Days of unsuppressed virus between baseline and 24 months	This measure will determine the days that subjects experience unsuppressed virus, measured between baseline and the end of the study at 24 months (continuous).	baseline, 24 months
Secondary	Achievement of = 90% adherence in month 24	This measure indicates whether subject achieved adherence of 90% or more during the final month of study participation in month 24 (dichotomous).	month 24
Secondary	Mean adherence from baseline through 24 months	This measure indicates mean adherence over the entire length of the study from enrollment through 24 months (continuous).	baseline through 24 months