NCT05040841

Brief 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).

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
534

participants targeted

Target at P75+ for not_applicable hiv-infections

Timeline
0mo left

Started Mar 2022

Longer than P75 for not_applicable hiv-infections

Geographic Reach
1 country

3 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress99%
Mar 2022Jun 2026

First Submitted

Initial submission to the registry

September 1, 2021

Completed
9 days until next milestone

First Posted

Study publicly available on registry

September 10, 2021

Completed
6 months until next milestone

Study Start

First participant enrolled

March 9, 2022

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 28, 2026

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2026

Expected
Last Updated

June 10, 2026

Status Verified

June 1, 2026

Enrollment Period

4.2 years

First QC Date

September 1, 2021

Last Update Submit

June 8, 2026

Conditions

Keywords

HIV treatmentHIV treatment adherenceRetention in careRandomized controlled trialFractional factorial designProctor implementation science frameworkCost-effectivenessSouth AfricaCommunity clinics

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • HIV viral suppression at 12 months

    12 months

  • Change in HIV viral load between baseline and 12 months

    baseline, 12 months

  • Change in HIV viral load between baseline and 24 months

    baseline, 24 months

  • Days of unsuppressed virus between baseline and 24 months

    baseline, 24 months

  • Achievement of ≥ 90% adherence in month 24

    month 24

  • +1 more secondary outcomes

Study Arms (16)

Condition 1

EXPERIMENTAL

Includes 1 intervention: S2/Peer: Enhanced peer group support.

Behavioral: S2/Peer: Enhanced peer group support

Condition 2

EXPERIMENTAL

Includes 1 intervention: S1/Text: Weekly check-in text messages.

Behavioral: S1/Text: Weekly check-in texts

Condition 3

EXPERIMENTAL

Includes 1 intervention: M3/EAM: Electronic adherence monitoring (EAM) + outreach to the patient.

Behavioral: M3/EAM: Immediate outreach to subject after EAM-identified missed doses

Condition 4

EXPERIMENTAL

Includes 3 interventions: M3/EAM: Electronic adherence monitoring (EAM) + outreach to the patient; S1/Text: Weekly check-in text messages; S2/Peer: Enhanced peer group support.

Behavioral: M3/EAM: Immediate outreach to subject after EAM-identified missed dosesBehavioral: S1/Text: Weekly check-in textsBehavioral: S2/Peer: Enhanced peer group support

Condition 5

EXPERIMENTAL

Includes 1 intervention: M2/PRM: Pharmacy refill monitoring (PRM) + outreach to the patient.

Behavioral: M2/PRM: Immediate outreach to subject after a missed pharmacy refill

Condition 6

EXPERIMENTAL

Includes 3 interventions: M2/PRM: Pharmacy refill monitoring (PRM) + outreach to the patient S1/Text: Weekly check-in text messages; S2/Peer: Enhanced peer group support.

Behavioral: M2/PRM: Immediate outreach to subject after a missed pharmacy refillBehavioral: S1/Text: Weekly check-in textsBehavioral: S2/Peer: Enhanced peer group support

Condition 7

EXPERIMENTAL

Includes 3 interventions: M2/PRM: Pharmacy refill monitoring (PRM) + outreach to the patient M3/EAM: Electronic adherence monitoring (EAM) + outreach to the patient; S2/Peer: Enhanced peer group support.

Behavioral: M2/PRM: Immediate outreach to subject after a missed pharmacy refillBehavioral: M3/EAM: Immediate outreach to subject after EAM-identified missed dosesBehavioral: S2/Peer: Enhanced peer group support

Condition 8

EXPERIMENTAL

Includes 3 interventions: M2/PRM: Pharmacy refill monitoring (PRM) + outreach to the patient; M3/EAM: Electronic adherence monitoring (EAM) + outreach to the patient; S1/Text: Weekly check-in text messages.

Behavioral: M2/PRM: Immediate outreach to subject after a missed pharmacy refillBehavioral: M3/EAM: Immediate outreach to subject after EAM-identified missed dosesBehavioral: S1/Text: Weekly check-in texts

Condition 9

EXPERIMENTAL

Includes 1 intervention: M1/OTR: Outreach (OTR) to patient due to unsuppressed VL test result.

Behavioral: M1/OTR: Immediate outreach to subject due to unsuppressed viral load test result

Condition 10

EXPERIMENTAL

Includes 3 interventions: M1/OTR: Outreach to patient due to unsuppressed VL test result; S1/Text: Weekly check-in text messages; S2/Peer: Enhanced peer group support.

Behavioral: M1/OTR: Immediate outreach to subject due to unsuppressed viral load test resultBehavioral: S1/Text: Weekly check-in textsBehavioral: S2/Peer: Enhanced peer group support

Condition 11

EXPERIMENTAL

Includes 3 interventions: M1/OTR: Outreach to patient due to unsuppressed VL test result; M3/EAM: Electronic adherence monitoring (EAM) + outreach to the patient; S2/Peer: Enhanced peer group support.

Behavioral: M1/OTR: Immediate outreach to subject due to unsuppressed viral load test resultBehavioral: M3/EAM: Immediate outreach to subject after EAM-identified missed dosesBehavioral: S2/Peer: Enhanced peer group support

Condition 12

EXPERIMENTAL

Includes 3 interventions: M1/OTR: Outreach to patient due to unsuppressed VL test result; M3/EAM: Electronic adherence monitoring (EAM) + outreach to the patient; S1/Text: Weekly check-in text messages.

Behavioral: M1/OTR: Immediate outreach to subject due to unsuppressed viral load test resultBehavioral: M3/EAM: Immediate outreach to subject after EAM-identified missed dosesBehavioral: S1/Text: Weekly check-in texts

Condition 13

EXPERIMENTAL

Includes 3 interventions: M1/OTR: Outreach to patient due to unsuppressed VL test result; M2/PRM: Pharmacy refill monitoring (PRM) + outreach to the patient; S2/Peer: Enhanced peer group support.

Behavioral: M1/OTR: Immediate outreach to subject due to unsuppressed viral load test resultBehavioral: M2/PRM: Immediate outreach to subject after a missed pharmacy refillBehavioral: S2/Peer: Enhanced peer group support

Condition 14

EXPERIMENTAL

Includes 3 interventions: M1/OTR: Outreach to patient due to unsuppressed VL test result; M2/PRM: Pharmacy refill monitoring (PRM) + outreach to the patient; S1/Text: Weekly check-in text messages.

Behavioral: M1/OTR: Immediate outreach to subject due to unsuppressed viral load test resultBehavioral: M2/PRM: Immediate outreach to subject after a missed pharmacy refillBehavioral: S1/Text: Weekly check-in texts

Condition 15

EXPERIMENTAL

Includes 3 interventions: M1/OTR: Outreach to patient due to unsuppressed VL test result; M2/PRM: Pharmacy refill monitoring (PRM) + outreach to the patient; M3/EAM: Electronic adherence monitoring (EAM) + outreach to the patient.

Behavioral: M1/OTR: Immediate outreach to subject due to unsuppressed viral load test resultBehavioral: M2/PRM: Immediate outreach to subject after a missed pharmacy refillBehavioral: M3/EAM: Immediate outreach to subject after EAM-identified missed doses

Condition 16

EXPERIMENTAL

Includes 5 interventions: M1/OTR: Outreach to patient due to unsuppressed VL test result; M2/PRM: Pharmacy refill monitoring (PRM) + outreach to the patient; M3/EAM: Electronic adherence monitoring (EAM) + outreach to the patient; S1/Text: Weekly check-in text messages; S2/Peer: Enhanced peer group support.

Behavioral: M1/OTR: Immediate outreach to subject due to unsuppressed viral load test resultBehavioral: M2/PRM: Immediate outreach to subject after a missed pharmacy refillBehavioral: M3/EAM: Immediate outreach to subject after EAM-identified missed dosesBehavioral: S1/Text: Weekly check-in textsBehavioral: S2/Peer: Enhanced peer group support

Interventions

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.

Also known as: S2/Peer
Condition 1Condition 10Condition 11Condition 13Condition 16Condition 4Condition 6Condition 7

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.

Also known as: M3/EAM
Condition 11Condition 12Condition 15Condition 16Condition 3Condition 4Condition 7Condition 8

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.

Also known as: M2/PRM
Condition 13Condition 14Condition 15Condition 16Condition 5Condition 6Condition 7Condition 8

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.

Also known as: M1/OTR
Condition 10Condition 11Condition 12Condition 13Condition 14Condition 15Condition 16Condition 9

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.

Also known as: S1/Text
Condition 10Condition 12Condition 14Condition 16Condition 2Condition 4Condition 6Condition 8

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Mzamomhle

Cape Town, Western Cape, South Africa

Location

Phumlani

Cape Town, Western Cape, South Africa

Location

Weltevreden Valley

Cape Town, Western Cape, South Africa

Location

Related Publications (1)

  • Jennings L, West RL, Halim N, Kaiser JL, Gwadz M, MacLeod WB, Gifford AL, Haberer JE, Orrell C, Sabin LL. Protocol for an evaluation of adherence monitoring and support interventions among people initiating antiretroviral therapy in Cape Town, South Africa-a multiphase optimization strategy (MOST) approach using a fractional factorial design. Trials. 2023 May 5;24(1):310. doi: 10.1186/s13063-023-07322-z.

MeSH Terms

Conditions

HIV InfectionsMedication Adherence

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesPatient CompliancePatient Acceptance of Health CareTreatment Adherence and ComplianceHealth BehaviorBehavior

Study Officials

  • Lora Sabin, PhD, MA

    Boston University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
FACTORIAL
Model Details: The investigators will randomize subjects to one of 16 conditions, using a fractional factorial design to determine the effects of five intervention components.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 1, 2021

First Posted

September 10, 2021

Study Start

March 9, 2022

Primary Completion

May 28, 2026

Study Completion (Estimated)

June 30, 2026

Last Updated

June 10, 2026

Record last verified: 2026-06

Data Sharing

IPD Sharing
Will not share

We have not yet made a detailed plan, but tentatively, we will deposit de-identified IPD in a repository at Boston University (BU) School of Public Health and the Desmond Tutu Health Foundation that can be made available to other researchers once our planned analyses are complete.

Locations