Effectiveness & Implementation of a Behavioral Intervention for Adherence and Substance Use in HIV Care in South Africa

Study Overview
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Brief Summary
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The purpose of this study is to test the effectiveness and implementation of a brief, integrated behavioral intervention for HIV medication adherence and substance use in the HIV care setting in South Africa. The intervention is specifically designed to be implemented by non-specialist counselors using a task sharing model in local HIV clinics. The behavioral intervention will be compared to usual care, enhanced with referral to a local outpatient substance use treatment program (Enhanced Standard of Care - ESOC) on study endpoints (as described in study endpoint section below).

Detailed Description
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The HIV epidemic in South Africa (SA) is among the highest in the world. SA has a large antiretroviral therapy (ART) program, but some individuals exhibit poor ART adherence, which increases the likelihood of developing drug resistance and failing the only available first and second line ART regimens in SA. ART nonadherence contributes to greater morbidity, mortality, and higher likelihood of sexual HIV transmission when virus is detectable. At the same time, alcohol and other drug use is prevalent among HIV-infected individuals in SA and associated with worse ART adherence, lower rates of viral suppression, and HIV transmission risk behavior. Yet, despite the impact of untreated substance use on poor HIV treatment outcomes and continued HIV transmission, there is little if any integration of substance use and HIV care services in SA, which creates a fragmented and incomplete system of care. This study had three phases, first being formative, qualitative work which led to a systematic treatment adaptation phase. This third phase, the clinical trial, is based on this formative work and other empirical support using behavioral interventions to improve ART adherence and reduce substance use in resource-limited settings, including SA. This study is a Type 1 hybrid effectiveness-implementation trial of a lay counselor-delivered behavioral intervention for adherence and substance use integrated into the HIV primary care setting in SA. To ensure that those who need this intervention most will receive it, participants will be patients with HIV who are struggling with adherence (as defined in the investigator's inclusion criteria) and who have an elevated substance use risk.

Official Title
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Hybrid Effectiveness-Implementation Trial for ART Adherence and Substance Use in HIV Care in South Africa

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

Intervention / Treatment
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* Behavioral: Project Khanya


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV positive and on ART 18-65 years of age Elevated substance use risk (ASSIST score greater than or equal to 4 for drugs or greater than or equal to 11 for alcohol) Have at least one of the following: Not attained viral suppression from first line ART (VL>400 copies/mL) On second-line ART treatment Reinitiated first-line treatment within the past three months Had a pharmacy non-refill at least once in the past 3 months Exclusion Criteria: Inability to provide informed consent or complete procedures in English or isiXhosa Severe risk/likely dependence for opiates (ASSIST score >26) because opiate substitution therapy may not be available Severe alcohol dependence symptoms that may warrant medical management of potential withdrawal symptoms Active, untreated, major mental illness (with untreated psychosis or mania) that would interfere with the paraprofessional adapted intervention

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Project Khanya<br>Those assigned to Project Khanya (the behavioral intervention for substance use and adherence condition) will have approximately 6 sessions (including Life-Steps, behavioral activation, and relapse prevention) delivered by a peer interventionist plus standard of care, which is typically referral to a local outpatient substance use treatment clinic. They will also receive a Wisepill, a wireless, real-time adherence monitoring device. | Behavioral: Project Khanya<br>* This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.<br>|
| No Intervention: ESOC<br>Those assigned to the ESOC (enhanced standard of care) condition will receive the standard of care, which is referral to a local substance use treatment clinic. The substance use clinics in the location that this study occurs follow the Matrix, and evidence-based 16-week outpatient program to treat substance use. We will enhance patients' normal referral to Matrix for ESOC participants by promoting facilitating and following up on the referral. Additionally, those in the control group will also receive a Wisepill, a wireless adherence monitoring device. | |

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 antiviral therapy agent (medications) taken as measured by real time wireless motoring device | Assessed between baseline assessment and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment) | 
| Biological Measure of Substance Use | Substance use measured with urinalysis. | Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment) | 
| Biological Measure of Substance Use | Substance use measured with phosphatidylethanol (PEth) concentration, which is an objective biomarker of alcohol use that can detect blood collected up to 21 days after alcohol consumption. Minimum detection value is 8 ng/mL. Higher PEth values indicate greater concentration of alcohol. Values of ≥ 50 ng/mL indicate unhealthy drinking. | Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment) | 
| Changes in Self-reported Substance Use | 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. | Assessed between baseline assessment and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biological Measure of Substance Use | Substance use measured with urinalysis. | Assessed at follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment) | 
| Biological Measure of Substance Use | Substance use measured with phosphatidylethanol (PEth) concentration, which is an objective biomarker of alcohol use that can detect blood collected up to 21 days after alcohol consumption. Minimum detection value is 8 ng/mL. Higher PEth values indicate greater concentration of alcohol. Values of ≥ 50 ng/mL indicate unhealthy drinking. | Assessed at follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment) | 
| Changes in Self-reported Substance Use | 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. | Assessed between baseline assessment and follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment) | 
| Intervention Acceptability | 15-item acceptability subscale of a pragmatic, quantitative assessment based on RE-AIM developed by the Applied Mental Health Research group (AMHR) at Johns Hopkins University. Total scores are averaged across all items and range from 0 to 3. Higher scores indicate greater acceptability. Qualitative interviews will also be conducted with intervention participants at the end of the study to assess acceptability guided by RE-AIM and the Proctor model. | Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment) | 
| Intervention Feasibility | 14-item feasibility subscale of a pragmatic, quantitative assessment based on RE-AIM developed by the Applied Mental Health Research group (AMHR) at Johns Hopkins University. Total scores are averaged across all items and range from 0 to 3. Higher scores indicate greater feasibility. Qualitative interviews will also be conducted with intervention participants at the end of the study to assess feasibility guided by RE-AIM and the Proctor model. | Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment) | 
| Intervention Fidelity | Independent fidelity ratings of a randomly selected subset (20%) of intervention sessions using a fidelity assessment developed for each session that includes 15-19 items that map onto each core intervention component, and factors unique to the peer delivery implementation strategy (i.e., appropriate self-disclosure, stigmatizing behaviors, common factors including warmth and non-judgment). | Assessed between randomization and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment) | 
| Intervention Uptake | Intervention participant attendance and retention (i.e., the mean number of intervention sessions attended by intervention participants) | Assessed between randomization and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunologic Deficiency Syndromes, Substance Use, Acquired Immunodeficiency Syndrome, Immune System Diseases, Behavioral Symptoms, RNA Virus Infections, HIV Infections, Alcohol Use, Drug Use