The CombinADO study to assess the impact of a combination intervention strategy on viral suppression, antiretroviral therapy adherence, and retention in HIV care among adolescents and young people living with HIV: protocol for a cluster-randomized controlled trial

Abstract

Background Adolescents and youth living with HIV (AYAHIV) have worse HIV outcomes than other age groups, particularly in sub-Saharan Africa (SSA). AYAHIV in SSA face formidable health system, interpersonal- and individual-level barriers to retention in HIV care, uptake of ART, and achievement of viral suppression (VS), underscoring an urgent need for multi-component interventions to address these challenges. This cluster-randomized control trial (cRCT) aims to evaluate the effectiveness and monitor implementation of a community-informed multi-component intervention (“CombinADO strategy”) addressing individual-, facility-, and community-level factors to improve health outcomes for AYAHIV. Methods This trial will be conducted in 12 clinics in Nampula Province, Northern Mozambique. All clinics will implement an optimized standard of care (control) including (1) billboards/posters and radio shows, (2) healthcare worker (HCW) training, (3) one-stop adolescent and youth-friendly services, (4) information/motivation walls, (5) pill containers, and (6) tools to be used by HCW during clinical visits. The CombinADO strategy (intervention) will be superadded to control conditions at 6 randomly selected clinics. It will include five additional components: (1) peer support, (2) informational/motivational video, (3) support groups for AYAHIV caregivers, (4) AYAHIV support groups, and (5) mental health screening and linkage to adolescent-focused mental health support. The study conditions will be in place for 12 months; all AYAHIV (ages 10–24 years, on ART) seeking care in the participating sites will be exposed to either the control or intervention condition based on the clinic they attend. The primary outcome is VS (viral load < 50 copies/mL) at 12 months among AYAHIV attending participating clinics. Secondary outcomes include ART adherence (self-reported and TDF levels) and retention in care (engagement in the preceding 90 days). Uptake, feasibility, acceptability, and fidelity of the CombinADO strategy during implementation will be measured. Trial outcomes will be assessed in AYAHIV, caregivers, healthcare workers, and key informants. Statistical analyses will be conducted and reported in line with CONSORT guidelines for cRCTs. Discussion The CombinADO study will provide evidence on effectiveness and inform implementation of a novel community-informed multi-component intervention to improve retention, adherence, and VS among AYAHIV. If found effective, results will strengthen the rationale for scale up in SSA. Trial registration ClinicalTrials.gov NCT04930367. Registered on 18 June 2021

Integrating Adolescent Mental Health into HIV Prevention and Treatment Programs: Can Implementation Science Pave the Path Forward?

“… Pre-post design Primary Depression, emotional regulation, trauma, anxiety, suicide/self-harm, substance misuse, wellness PHQ-9, SSQ Shona symptoms questionnaire Trauma-ex, GAD-7, AUDIT Understanding and measuring the impact of stigma on PrEP adherence among adolescent girls and young women in Kenya: identifying targets for future interventions Kenya [ 46 ] Both Community based and clinic/hospital Improve understanding of stigma-related barriers to PrEP adherence Mixed Methods Exploratory Depression, anxiety, wellness PHQ-4, *RS-14 SMART: S trengthening M ental health A nd R esearch T raining ClinicalTrials.gov Identifier: NCT03081195 Kenya, Uganda and Ghana [ 76 ] AHISA School A scale-up longitudinal experimental study that uses a mixed-methods, hybrid type II, effectiveness implementation design to test the effectiveness of an EBP, called Multiple Family Group (MFG) for school children, young adolescents 8–13 y/o Randomized controlled trial, parallel Primary Depression, anxiety SDQ, CDI (child depression inventory, Tennessee self-concept Parent CES-D, Brief Symptom Checklist, and parent stress index short form ​DiSC (Data-informed Stepped Care) ClinicalTrials.gov Identifier: NCT05007717 Kenya [ 77 ] Both Clinic/hospital The data-informed stepped care (DiSC) intervention pairs stepped care with a clinical prediction tool to optimize limited resources and improve HIV care and treatment outcomes. Randomized controlled trial, parallel Exploratory Depression, anxiety, substance misuse PHQ-9, GAD-7, AUDIT ​​CombinADO (Combination intervention strategy to improve health outcomes for adolescents) ClinicalTrials.gov Identifier: NCT04930367 Mozambique [ 36 , 78 ] PATC3H …”

Positive attitudes toward adoption of a multi-component intervention strategy aimed at improving HIV outcomes among adolescents and young people in Nampula, Mozambique: perspectives of HIV care providers

“…A detailed description of study interventions and methods of the CombinADO trial has previously been published elsewhere [ 37 ]. Briefly, the CombinADO intervention strategies have been developed as a response to the National Institute of Child Health and Development (NICHD) call for more research towards generating needed evidence on effective public health interventions for young people affected by HIV in resource-limited settings, the Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource-Constrained Settings (PATC 3 H) program [ 39 ].…”

Human-Centered Design for Public Health Innovation: Codesigning a Multicomponent Intervention to Support Youth Across the HIV Care Continuum in Mozambique

“…In Phase 2, a cluster-randomized control trial will be used to evaluate the effectiveness of the CombinADO intervention in increasing retention in care, ART adherence, and viral suppression at 12 health clinics in Nampula (clinicaltrials.gov: NCT04930367). 30…”

“…The HCD approach is not designed to evaluate efficacy or effectiveness but can be rigorously evaluated via randomized control trials. 30,46 Furthermore, the final intervention may have limited generalizability since data are collected via purposive sampling to be contextually specific. However, the intervention may be transferred and inform intervention development in other settings.…”