Choice-Based Support for Adults Starting or Restarting Antiretroviral Therapy in Cape Town, South Africa (Zikhethele)

Zikhethele - Choose For You Aim 3 Exploring the Feasibility, Acceptability and Preliminary Impact of Choice-based Antiretroviral Therapy (ART) Support Interventions for Adults Starting and Restarting ART in Cape Town, South Africa: A Pilot Randomised Controlled Trial

Disengagement from HIV care is very common in the first year after starting or restarting antiretroviral therapy (ART). There is increasing recognition of people cycling in and out of HIV care over time people newly starting and restarting treatment after an interruption are at high risk of subsequent disengagement from care. While guidelines advocate for patient-centered models of care, patient preferences are often not considered fully in the design of interventions. Building on existing support intervention modalities, formative qualitative research and a stated preference survey, the investigators have designed a choice-based ART support intervention. The intervention offers a choice of a) in-person group support, b) low-touch WhatsApp support group, and c) individual digital support through the AI Coach chatbot.

This study will explore the feasibility, acceptability and preliminary impact of choice-based ART support for adults starting and restarting ART in Cape Town, South Africa, through a randomized pilot feasibility trial.

The objectives of this study are:

1. To determine the feasibility, acceptability, appropriateness and fidelity of the Zikhethele intervention components, including offering patients a choice of ART support intervention.
2. To describe the distribution of actual choices in the choice arm.
3. To describe outcomes in each pilot trial arm and explore the preliminary impact of offering a choice, compared allocation to a support intervention or standard of care, on patient empowerment and treatment outcomes.
4. To explore the hypothesised mechanisms of action and contextual moderators through in-depth interviews with participants and providers including consideration of patient empowerment, stigma and social support, and trust in provider, peers and digital tools.

A total of 140 adults starting or restarting ART will be consecutively recruited and randomised to a) standard of care (n=35), b) in-person support (n=35) and c) a choice (n=70) of in-person support, WhatsApp group support, AI coach, or no additional support (standard of care).

The intervention components will run for the first four months after start or restart, through to the first viral load and eligibility assessment for routine differentiated models of care. Briefly, the in-person group support will consist of monthly informal and discussion-based sessions framed around chronic medication adherence (including HIV, diabetes, and hypertension), designed to create a safe and supportive space where participants can share experiences, problem-solve, and build motivation to remain in care. The WhatsApp group support will be a virtual adaptation of the in-person model, designed to provide an accessible, low-barrier option for participants who prefer remote or flexible engagement. The AI Coach is a pilot AI chatbot (developed by Audere, PSI, HSRC, and Matchboxology, and being piloted in Gauteng and KwaZulu Natal by HE2RO at the Wits Health Consortium) inspired by the in-person Coach Mpilo model-a peer navigator case management approach in South Africa that employs men living with HIV as "coaches" to support linkage, retention, and re-engagement in care. The AI coach is available anytime via WhatsApp, and offers trusted information (through a curated large-language model), and empathetic counselling and behavioural nudges to encourage healthy habits.

Individuals (aged 18 and older, living with HIV and currently attending the clinic to start ART for the first time or to restart after an interruption of 3 or more months) will be approached during their routine clinic visit by a trained research fieldworker. Eligible individuals will undergo informed consent and be enrolled. Participants will complete an interviewer administered questionnaire at enrolment and at four months. Outcome data will also be abstracted from paper and electronic medical records, as well study and intervention logs, intervention debriefings and chatbot logs. A subset of 20 participants, purposefully selected to include each intervention component, will be invited to complete an in-depth interview at 4 months. Providers (n=6), while not involved directly in this pilot implementation, will also be invited to participate in an in-depth interview to explore the potential of this intervention.

This exploratory pilot study serves as a proof-of-concept for offering people living with HIV different modalities of support for engagement in care in the first four months. The study is not powered for efficacy but will provide valuable insights into feasibility (of both the trial design and intervention components) and acceptability, as well as real-world preferences and trade-offs. The investigators hypothesize that those able to choose a support intervention most appealing or most fitting to their life circumstances may have improved health empowerment which may in turn improve health outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Care Loss to Followup
• Intervention / Treatment: Behavioral: In-person group support; Behavioral: WhatsApp group support; Behavioral: AI coach; Behavioral: Choice of support

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tamsin K Phillips, MPH, PhD; Phone Number: +27216501646; Email: tammy.phillips@uct.ac.za

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa
      • Gugulethu Community Health Centre
      • Contact: Tamsin K Phillips, MPH, PhD; Phone Number: +27216501646; Email: tammy.phillips@uct.ac.za

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or older
• Living with HIV
• Starting ART for the first time or restarting ART after an interruption of at least three months
• Eligible to start or restart ART based on local guidelines
• Clinically stable (no acute illness or evidence of TB/meningitis)
• English or isiXhosa speaking
• Willing and able to provide informed consent to participate.

Exclusion Criteria:

- Pregnancy at the time of enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care support; Participants allocated to the standard of care arm will receive no additional adherence support. Following ART start or restart, they will be supported per standard of care in the routine services. This includes follow-up after missed visits and additional counselling should any challenges be flagged by providers.
Experimental: In-person group support; Participants allocated to the in-person group support arm will receive the usual standard of care support, and will also be enrolled into an in-person support group (described in detail in the intervention description).	Behavioral: In-person group support; The in-person group is framed around chronic medication adherence (including HIV, diabetes, and hypertension). It will consist of monthly informal and discussion-based sessions (60-90 minutes) designed to create a safe and supportive space where participants can share experiences, problem-solve together, and build motivation to remain in care. The group seeks to provide a semi-structured, peer-supported environment. Groups will consist of maximum 15 people. Participants will not be provided with any transport costs or reimbursement as this would not be feasible to scale. Tea and coffee and light refreshments will be provided. Each participant will be able to attend a minimum of three sessions over a four-month period. Sessions will be supported by a trained facilitator (peer living with a chronic health condition).
Experimental: Choice of support; Participants allocated to the choice arm will be offered a structured choice of adherence support and asked to select the modality that best fits their needs and circumstances. The choice process will be facilitated by a trained community health worker, who will also support coordination and enrolment into the selected option. The choice options (described in detail in the intervention descriptions) are: In-person group support, WhatsApp group support, AI coach, No support (standard of care support only)	Behavioral: In-person group support; The in-person group is framed around chronic medication adherence (including HIV, diabetes, and hypertension). It will consist of monthly informal and discussion-based sessions (60-90 minutes) designed to create a safe and supportive space where participants can share experiences, problem-solve together, and build motivation to remain in care. The group seeks to provide a semi-structured, peer-supported environment. Groups will consist of maximum 15 people. Participants will not be provided with any transport costs or reimbursement as this would not be feasible to scale. Tea and coffee and light refreshments will be provided. Each participant will be able to attend a minimum of three sessions over a four-month period. Sessions will be supported by a trained facilitator (peer living with a chronic health condition).; Behavioral: WhatsApp group support; The WhatsApp group support will be a virtual adaptation of the in-person group support model, designed to provide an accessible, low-barrier option for participants who prefer remote or flexible engagement. The group is framed as a virtual support community for people living with chronic health conditions such as HIV, diabetes, or hypertension. The group size will be 15-20 people. This virtual space aims to maintain the benefits of peer connection and mutual motivation while minimizing logistical and social barriers to participation. It builds on growing evidence for mHealth peer support in ART adherence and retention interventions in South Africa. Participants will be added to a single WhatsApp group called Zikhethele, moderated by a trained community health worker. The group will remain active for approximately four months, mirroring the duration of the in-person group. Members may join or leave the group at any time.; Behavioral: AI coach; AI coach (developed by Population Services International (PSI), Wits Health Consortium (WCI), and Audere) is a digital version of the in-person Coach Mpilo model where a peer navigator case management approach in South Africa that employs men living with HIV as "coaches" to support linkage, retention, and re-engagement in care. The digital version is an AI-based chatbot over WhatsApp, which aims to replicate the motivational, supportive functions of a human coach. The AI coach is available anytime, anywhere via WhatsApp, and offers trusted information (through a curated large-language model), and empathetic counselling and behavioural nudges to encourage healthy habits. Users are able to engage with the chatbot on their own phone or other device, via WhatsApp, at any time, from any location, free of charge (other than the use of WhatsApp data). The chatbot is not structured or scripted but rather designed to respond to any question or statement posed by the user.; Behavioral: Choice of support; Participants will receive a brief description of the available support options (in-person club, WhatsApp group, or AI coach) following a standard script. They will be able to discuss and select the modality that best fits their needs and circumstances. Participants in the choice arm will be asked to select one of the available intervention options, or they will be able to choose not to sign up for additional ART support (standard of care). The choice process will be facilitated by a trained community health worker, who will also support coordination and enrolment into the selected option. Offering choice has the potential to promote patient empowerment, strengthen engagement in care, and optimize treatment outcomes. Allowing patients to select a preferred health intervention, this can increase satisfaction, self-efficacy and health care empowerment, which in turn may improve engagement and health outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intervention fidelity: intervention completion	% completion of intervention components	Through study completion, on average four months
Experiences and perceptions of receiving or implementing the intervention	Themes in in-depth-interviews and open-ended responses: practicality and resources for implementation.	Through study completion, on average four months
Intervention acceptability	Experiences and perceptions of receiving or implementing the intervention. Themes: satisfaction, preferences, benefits and risks, and relevance for context from in-depth interviews and open-ended survey questions.	Assessed at month 4
Recruitment feasibility: Refusals	Number of of eligible participants refusing participation	Through end of recruitment, expected duration one month
Retention in study	% enrolled participants completing the four month interview	Through study completion, an average of four months
Study measurement feasibility: Interview completion	Number of enrolled participants not completing or partially completing study measures	Through study completion, an average of four months
Patient empowerment	Qualitative interviews Health Care Empowerment Inventory: 8-item scale separated into "informed, committed, collaborative, engaged" and "tolerance of uncertainty" subscales. Each item scored from 1-5. Each sub scale has a maximum score of 20 and a minimum of 4. Higher scores indicated higher levels of empowerment.	Enrolment and month 4
Perceived Availability of Social Support	7-item scale used to assess the perceived availability of instrumental and emotional social support. Each item scored from 1-5 (minimum score 7, maximum 35). Higher scores indicate higher levels of social support.	Enrolment and month 4
Social Impact Scale	7-item scale used to assess HIV-related stigma, including social rejection (2 items, minimum score 2, maximum score 10) and internalized stigma (5 items, minimum score 5, maximum score 25). Each item scored from 1-5. Higher scores indicate higher levels of stigma.	Enrolment and month 4
Health Care Relationship Trust Scale	13-item scale assessing participants trust in their HIV provider. Each item scored 0-4. Minimum score 0, maximum score 52. Higher scores indicate higher levels of trust in the health provider.	Enrolment and month 4
Start/restart perceptions	Description of themes from qualitative interviews and open-ended survey questions assessing ease of ART start or restart along with barriers and enablers.	At month 4
Feasibility of Intervention Measure (FIM)	Four item scale with values ranging from 1-completely disagree to 5-completely agree. Higher scores indicate high feasibility.	Assessed at month 4
Choice of support	Number choosing each support option and number participating in the chosen support	Through study completion, on average four months
Safety	Report of any privacy/safety events through the interventions or study measurement data collection.	Through study completion, on average four months
Acceptability of Intervention Measure (AIM)	Four item scale with values ranging from 1-completely disagree to 5-completely agree. Higher scores indicated higher acceptability.	Assessed at month 4
Recruitment feasibility: time to complete recruitment	Documenting time to complete recruitment along with periods when unable to recruit.	Through end of recruitment, expected duration one month
Study measurement feasibility: Interview length	Average time to complete measurement interviews	Through study completion, an average of four months
Study measurement feasibility: user-engagement data	Frequency and type of intervention user-engagement data not accessed for interventions along with reasons for delay or lack of access	Through study completion, an average of four months
Intervention fidelity: User engagement	Frequency and context of engagement with each intervention component.	Through study completion, an average of four months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention in HV care	in care with no ART interruption 4 months after start/restart collected through interview and medical records.; in care with no ART interruption 6 and 12 months after start/restart collected through medical records.	Month 4 and month 12
Intervention adaptations	Documented challenges and resulting adaptations emerging from weekly intervention debriefing discussions	Through study completions, an average of four months
HIV viral load suppression	virally suppressed at 3 months after start/restart based on medical records; virally suppressed at 12-18 months after start/restart based on medical records	Month 3 and month 12
HIV self-management	Four item scale measuring reported self regulation in medication taking. Each item scored 1-5 (minimum 4, maximum 20). Higher scores indicate better self-management.	Month 4
Self-reported ART adherence	3-item self-reported adherence scale assessing adherence in the past 30 days	Month 4

Collaborators and Investigators

• Sponsor: University of Cape Town
• Collaborators: National Institute of Mental Health (NIMH); Fogarty International Center of the National Institute of Health

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: HIV; antiretroviral therapy; patient choice; engagement in care; adherence support
• Other Study ID Numbers: K43TW011943 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data that underlie the primary and secondary outcome analyses of this pilot randomised trial will be shared where feasible. These data may include trial arm assignment, baseline characteristics, outcome measures, and derived variables used in published analyses.

Certain individual-level data will not be shared due to ethical constraints and limitations in the ability to adequately de-identify the data, particularly given the small sample size and sensitive contextual information. Data excluded from sharing may include variables that pose a risk of re-identification or deductive disclosure.

IPD Sharing Access Criteria

Where appropriate, de-identified data will be:

• Deposited in a publicly accessible data repository, or
• Made available as supplementary material accompanying peer-reviewed publications.

If open public release is not feasible due to POPIA or ethics restrictions, data will be shared via a controlled-access mechanism. Access will be granted upon reasonable request and subject to approval by the study team and, where applicable, the relevant ethics committee.

Data will be shared for research purposes only, in accordance with the Protection of Personal Information Act (POPIA). Data users will be required to:

• Agree not to attempt to re-identify participants
• Use the data only for the approved purpose
• Cite the original study appropriately
• Comply with applicable data protection and governance requirements

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No