The 'Comprehensive Adherence Resource and Empowerment Support' (CARES) Study (CARES)

Adapting the 'Comprehensive Adherence Resource and Empowerment Support' Intervention for Multiple PrEP Methods Among Adolescent Girls and Young Women in South Africa and Zimbabwe

The primary aim of this study is to adapt the Comprehensive Adherence Resource and Empowerment Support (CARES) intervention to support adolescent girls and young women (AGYW) aged 16-24 in Zimbabwe and South Africa in effectively using various forms of pre-exposure prophylaxis (PrEP), specifically oral, ring, and injectable PrEP. Originally developed for a clinical trial setting, CARES has shown promising results in enhancing effective PrEP use through a structured mix of counseling, SMS/phone calls, and peer support for daily oral PrEP and the PrEP ring. However, its resource-intensive design requires adaptation for routine public health settings to ensure feasibility, fidelity, acceptability, and effectiveness. This adapted intervention will be tailored with input from AGYW, PrEP providers, and local stakeholders to support sustainable PrEP use and address HIV prevention needs among AGYW. Additionally, it will incorporate injectable PrEP and be modified to suit routine public health contexts. Once the components are finalized, the adapted CARES intervention will be evaluated for effectiveness, feasibility, fidelity, and acceptability.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV
• Intervention / Treatment: Behavioral: Comprehensive Adherence Resource and Empowerment Support' (CARES)

• Study Type: Interventional
• Enrollment (Estimated): 2100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah Roberts, PhD; Phone Number: +1919-541-6000; Email: sroberts@rti.org

Study Locations

• South Africa
  • Cape Town, South Africa
    • Desmond Tutu Health Foundation
    • Contact: Millicent Atujuna, PhD; Phone Number: +27 825187551; Email: millicent.atujuna@hiv-research.org.za
    • Principal Investigator: Millicent Millicent Atujuna, PhD
• Zimbabwe
  • Harare, Zimbabwe
    • Pangaea Zimbabwe
    • Contact: Nyaradzo Mavis Mgodi, MBChB, MMed; Phone Number: +263 772264616; Email: nmgodi@uz-ctrc.org
    • Principal Investigator: Nyaradzo Mavis Mgodi, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Aim 2:

Inclusion (AGYW):

• age 16-24 years (in Zimbabwe, participants aged 16 to 17 years must meet the legal criteria for emancipation to be eligible)
• has initiated PrEP during the study, or no more than 6 months before the study initiation date (for LEN PrEP), or no more than 3 months before the study initiation date (for oral, ring, or CAB PrEP), and
• willing and able to provide written informed consent for access to medical records, or assent and parental consent if applicable
• fluent in one of the study languages (English, isiXhosa, Shona, Ndebele)
• target date for PrEP resupply (i.e., to ensure continued coverage) falls within the month.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Comprehensive Adherence Resource and Empowerment Support (CARES); Each health facility will initially offer standard of care (SOC) adherence counseling, then will transition on a randomly assigned start date to offering the CARES intervention instead of SOC adherence counseling. Choice of available PrEP methods will be available throughout the study as part of standard of care at the health facilities.

Behavioral: Comprehensive Adherence Resource and Empowerment Support' (CARES); The CARES intervention includes one-on-one client-centered adherence counseling, objective adherence feedback, and optional support strategies selected according to participant needs and preferences, such as two-way SMS reminders, weekly check-ins, peer buddy support, and adherence clubs. The final intervention package will be adapted for study implementation during the formative phase of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of AGYW receiving on-time PrEP resupply [PrEP continuation]	Percent of AGYW per clinic per month who have received on-time PrEP resupply at all scheduled visits for 3 months after initiation for CAB injection, oral PrEP, and ring or 6 months after initiation for LEN injection. Measured among those due for resupply visit in that month. On-time resupply is defined as resupply within a 14-day window of the target date to ensure continuous coverage.	Monthly for 27 months from the start of the pre-intervention period to the end of the intervention delivery period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with high PrEP adherence [High PrEP adherence]	Percent of subsample participants per clinic per month with (1) biomarker TFVdp levels indicating consistent use (≥700 fmol/punch, corresponding to 4 doses per week) for the past 1-2 months; (2) >4mg Dapivirine released from used PrEP rings, indicating consistent use for the past 4 weeks; or (3) clinical records indicating on-time injection of injectable PrEP	Monthly for a total of 21 months, from the start of the pre-intervention period to the end of the intervention delivery period with a pause during the 6-month washout period after the start of intervention delivery.

Collaborators and Investigators

• Sponsor: RTI International
• Collaborators: National Institute of Mental Health (NIMH); University of Chicago; Pangaea Zimbabwe Aids Trust; Desmond Tutu Health Foundation
• Investigators: Principal Investigator: Sarah Roberts, PhD, RTI International; Principal Investigator: Millicent Atujuna, PhD, Desmond Tutu Health Foundation; Principal Investigator: Nyaradzo Mavis Mgodi, MBChB, MMed, Pangaea Zimbabwe Aids Trust

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 18, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Feasibility; PrEP; South Africa; Effectiveness; Acceptability; Fidelity; Zimbabwe; AGYW
• Other Study ID Numbers: HREC-020/2025; MRCZ/A/3293; R01MH137804 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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