Project Khanya: Peer-Delivered Intervention to Improve HIV Medication Adherence and Substance Use in South Africa

Study Overview
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Brief Summary
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The purpose of this study is to evaluate a stepped care behavioral intervention for HIV medication adherence and substance use (Khanya) integrated into an HIV primary care setting in South Africa. The intervention is specifically designed to be implemented by non-specialist counselors with lived substance use experience (i.e., peers), using a task sharing, stepped care model in local primary care clinics. The Khanya stepped care package will be compared to usual care, enhanced with referral to a local outpatient substance use treatment program (Enhanced Standard of Care - ESOC) over 12 months.

Detailed Description
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South Africa is home the highest number of people living with HIV in the world and has a high burden of substance use disorder (SUD). Globally, a SUD treatment gap exists, particularly in low and middle-income countries (LMICs), such as South Africa, where only 1-4% of individuals receive minimally adequate treatment. Workforce shortages are also severe in LMICS, and countries such as South Africa have responded to this through the implementation of task sharing models to expand access to antiretroviral therapy (ART) and mental health services. However, efforts to implement task shared, SUD treatment and ART adherence interventions that can be feasibly and sustainably integrated into primary care are limited. Therefore, the purpose of this study is to help fill this gap in care by evaluating Khanya, a peer-delivered, behavioral intervention to improve HIV care outcomes and reduce substance use. The present study is a hybrid effectiveness-implementation trial designed to evaluate Khanya compared to usual care, enhanced with referral to a local outpatient substance use treatment program (Enhanced Standard of Care - ESOC) over 12 months. To provide care for those most in need, participants will be patients with HIV who are struggling with ART adherence and have elevated SUD risk. In this study, Khanya will be delivered as a stepped-care package in which the least resource-intensive part of the intervention (i.e., a single session problem solving intervention for HIV medication adherence) will be delivered first. Only individuals randomized to the Khanya intervention who are still struggling with HIV medication adherence after the first session will be stepped up to receive the more comprehensive, resource-intensive part of the intervention (i.e., six additional sessions of the intervention). Primary effectiveness outcomes in this clinical trial include ART adherence and SUD.

Official Title
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A Stepped Care, Peer-Delivered Intervention to Improve ART Adherence and SUD in Primary Care

Conditions
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Human Immunodeficiency Virus, Alcohol-Related Disorders, Drug Use, Substance Use

Intervention / Treatment
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* Behavioral: Khanya


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV positive and on ART ≥18 years of age At least moderate substance use risk in the past 3 months for at least one non-tobacco substance (measured by the WHO- ASSIST: score ≥11 for alcohol, ≥4 for non-tobacco drugs) ART nonadherence and/or risk of virologic failure, defined as at least one of the following in the past 12 months 1) re-engaging in care after ≥1 month of being out of care (confirmed by pharmacy refill data) 2) ≥1 episodes of VL >400 copies/mL 3) on second- or third-line ARTs. Exclusion Criteria: Severe risk/likely dependence for opiates (WHO ASSIST score >26) because opiate substitution therapy is largely not available Severe alcohol dependence symptoms that may warrant medical management of potential withdrawal symptoms/stabilization prior to study participation Inability to provide informed consent or complete study procedures in isiXhosa or English In third trimester of pregnancy during baseline Currently enrolled in another study or treatment program focused on substance use (including Matrix) or ART adherence. Untreated or undertreated major mental illness that would interfere with study procedures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Khanya<br>Khanya is a peer-delivered, behavioral intervention to improve HIV medication adherence and reduce problematic SUD symptoms. Khanya is delivered as a stepped-care package in which the least resource-intensive part of the intervention (i.e., Life-Steps, a single session problem solving intervention for HIV medication adherence) will be delivered first. Only individuals randomized to the Khanya intervention who are still struggling with HIV medication adherence after the first session will be stepped up to receive the more comprehensive, resource-intensive part of the intervention (i.e., six additional sessions of the intervention). Khanya Step 2 includes evidence-based treatment components to improve ART adherence and SU, including motivational interviewing, behavioral activation, and mindfulness-based relapse prevention strategies, which have previously been piloted in this community. | Behavioral: Khanya<br>* Khanya is a peer-delivered, behavioral intervention to improve HIV medication adherence and reduce problematic SUD symptoms. Participants will either receive Khanya Step 1 or if they continue to struggle with ART adherence, they will be stepped up to the more intensive intervention, Khanya Step 2.<br>|
| No Intervention: Enhanced Standard of Care (ESOC)<br>Enhanced Standard of Care (ESOC) includes the local standard of care, which is referral to a free local outpatient substance use treatment program, enhanced with facilitated referrals. To enhance the standard of care, study staff will provide participants with a detailed description of the program's referral process and offer to help the participant set up an intake at the program. Additionally, the team will follow up on the referral. Participants in this arm will also receive Wisepill, a wireless adherence monitoring advice, at the baseline assessment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in HIV Medication Adherence Throughout Intervention Phase | Percentage of prescribed antiretroviral therapy (medications) taken as measured by real time wireless monitoring device | Assessed between baseline and 3-month assessment | 
| Biological Measure of Substance Use After intervention | Urine toxicology-verified substance use at the acute post-intervention assessment. | 3-month assessment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in HIV Medication Adherence Over Follow-Up | Percentage of prescribed antiretroviral therapy (medications) taken as prescribed measured using real-time wireless monitoring (Wisepill) | Aggregate across 3-, 6-, and 12-month assessments | 
| Biological Measure of Substance Use Over Follow-Up | Urine toxicology-verified substance use | Aggregate across 3-, 6-, and 12-month assessments | 
| Changes in Self-Reported Substance Use | Self-reported substance use will be assessed primarily by the World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test (WHO-ASSIST). It is a measure used to assess substance use risk for alcohol, cannabis, cocaine, opiates, and amphetamines, hallucinogens, and other drugs. Standardized cutoff scores are used to categorize risk levels: low risk (0-3 for illicit drugs/0-10 for alcohol), moderate risk (4-26 for illicit drugs/11-26 for alcohol), or high risk (> 26) for substance use-related problems. | Aggregate across 3-, 6-, and 12-month assessments | 
| Biological Measure of Adherence | Biomarker-confirmed ART adherence will be measured with Dried Blood Spot (DBS) analysis of tenofovir diphosphate (TDF-DiP). | Aggregate across 3-, 6-, and 12-month assessments | 
| HIV Clinic Attendance | Number of days participants in each condition were on-time to, late to, or missed an HIV clinic appointment (extracted from clinic records). | Aggregate across 3-, 6-, and 12-month assessments | 
| HIV Viral Load | Percentage of patients with a detectable viral load | Aggregate across 3-, 6-, and 12-month assessments | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunologic Deficiency Syndrome, Substance Use, Acquired Immunodeficiency Syndrome, Immune system diseases, behavioral symptoms, RNA Virus Infections, HIV Infections, Alcohol Use, Drug Use, Treatment Adherence and Compliance, Delivery and Health Care, Task Sharing, Mental Health, Global Health, South Africa, Cost Effectiveness, Implementation Science