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

• Sponsor: University of Maryland, College Park (Other)
• Overall Status: Completed
• CT.gov ID: NCT03529409
• Collaborator: University of Cape Town (Other), National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 66
• Locations: 2
• Arms: 2
• Actual Duration (Months): 20.3
• Patients Per Site: 33
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus; Alcohol-Related Disorders; Drug Use	Behavioral: Project Khanya	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hybrid Effectiveness-Implementation Trial for ART Adherence and Substance Use in HIV Care in South Africa
• Actual Study Start Date: Jul 30, 2018
• Actual Primary Completion Date: Feb 12, 2020
• Actual Study Completion Date: Apr 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Project Khanya 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; This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.
No Intervention: ESOC 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.

Outcome Measures

Primary Outcome Measures

1. Changes in HIV Medication Adherence Throughout Intervention Phase [Assessed between baseline assessment and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)]

   Percentage of prescribed antiviral therapy agent (medications) taken as measured by real time wireless motoring device

2. Biological Measure of Substance Use [Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)]

   Substance use measured with urinalysis.

3. Biological Measure of Substance Use [Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)]

   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.

4. Changes in Self-reported Substance Use [Assessed between baseline assessment and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)]

   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.

Secondary Outcome Measures

1. Biological Measure of Substance Use [Assessed at follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)]

   Substance use measured with urinalysis.

2. Biological Measure of Substance Use [Assessed at follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)]

   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.

3. Changes in Self-reported Substance Use [Assessed between baseline assessment and follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)]

   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.

4. Intervention Acceptability [Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)]

   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.

5. Intervention Feasibility [Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)]

   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.

6. Intervention Fidelity [Assessed between randomization and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)]

   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).

7. Intervention Uptake [Assessed between randomization and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)]

   Intervention participant attendance and retention (i.e., the mean number of intervention sessions attended by intervention participants)

Other Outcome Measures

1. HIV Viral Load [Assessed at follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)]

   Percentage of patients with a suppressed viral load (<400 copies/ml)

2. Changes in Self-reported Substance Use [Assessed between baseline assessment and follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)]

   Changes in percent days used any substance measured by timeline follow-back

3. Changes in Self-reported Substance Use [Assessed between baseline assessment and follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)]

   Changes in number of drinks measured by timeline follow-back

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. Not attained viral suppression from first line ART (VL>400 copies/mL)

2. On second-line ART treatment

3. Reinitiated first-line treatment within the past three months

4. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland	College Park	Maryland	United States	20742
2	University of Cape Town	Cape Town		South Africa	7700

Sponsors and Collaborators

• University of Maryland, College Park
• University of Cape Town
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Jessica F Magidson, PhD, University of Maryland

Study Documents (Full-Text)

• Study Protocol - Jun 1, 2020
• Statistical Analysis Plan - Dec 9, 2019

More Information

Publications

None provided.

• Responsible Party: Jessica Magidson, Assistant Professor, University of Maryland, College Park
• ClinicalTrials.gov Identifier: NCT03529409
• Other Study ID Numbers: 187/2018; K23DA041901
• First Posted: May 18, 2018
• Last Update Posted: May 18, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jessica Magidson, Assistant Professor, University of Maryland, College Park: Immunologic Deficiency Syndromes; Substance Use; Acquired Immunodeficiency Syndrome; Immune System Diseases; Behavioral Symptoms; RNA Virus Infections; HIV Infections; Alcohol Use; Drug Use
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Substance-Related Disorders; Alcohol-Related Disorders

Study Results

Participant Flow

Arm/Group Title	Project Khanya	ESOC	Pre-Randomization
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.	Participants enrolled in the study at the baseline assessment, but who were never randomized (approximately 2 weeks post-baseline) and therefore did not continue with the study.
Period Title: Randomized
STARTED	30	31	5
COMPLETED	30	31	0
NOT COMPLETED	0	0	5
Period Title: Randomized
STARTED	30	31	0
COMPLETED	26	26	0
NOT COMPLETED	4	5	0
Period Title: Randomized
STARTED	28	30	0
COMPLETED	27	29	0
NOT COMPLETED	1	1	0

Baseline Characteristics

Arm/Group Title	Project Khanya	ESOC	Pre-Randomization	Total
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.	Participants enrolled in the study at the baseline assessment, but who were never randomized (approximately 2 weeks post-baseline) and did not continue with the study.	Total of all reporting groups
Overall Participants	30	31	5	66
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.80 (10.47)	34.29 (7.99)	31.60 (9.56)	36.59 (9.66)
Sex: Female, Male (Count of Participants)
Female	13 43.3%	20 64.5%	3 60%	36 54.5%
Male	17 56.7%	11 35.5%	2 40%	30 45.5%
Race/Ethnicity, Customized (Count of Participants)
Black African	29 96.7%	31 100%	5 100%	65 98.5%
Mixed race	1 3.3%	0 0%	0 0%	1 1.5%
Region of Enrollment (participants) [Number]
South Africa	30 100%	31 100%	5 100%	66 100%
HIV medication adherence (percentage of days adherent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of days adherent]	53.6 (32.1)	49.3 (29.8)	46.60 (31.56)
Positive alcohol or drug urine test result (Count of Participants)
Count of Participants [Participants]	27 90%	29 93.5%	4 80%	60 90.9%
Phosphatidylethanol (PEth) concentration (ng/ML) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ML]	686.0 (639.9)	456.1 (530.8)	370.8 (418.4)	554.1 (582.0)
Moderate or high-risk on Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) measure (Count of Participants)
Count of Participants [Participants]	30 100%	31 100%	5 100%	66 100%
Suppressed viral load, <400 copies/ml (Count of Participants)
Count of Participants [Participants]	15 50%	24 77.4%	3 60%	42 63.6%
Consumed any substance on timeline followback (percentage of days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of days]	38.81 (24.58)	29.49 (21.72)	42.86 (35.36)	37.74 (24.29)
Number of drinks on days drinking on timeline followback (number of drinks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of drinks]	7.17 (3.79)	8.03 (5.59)	5.37 (6.24)	7.43 (4.86)

Outcome Measures

1. Primary Outcome

Title	Changes in HIV Medication Adherence Throughout Intervention Phase
Description	Percentage of prescribed antiviral therapy agent (medications) taken as measured by real time wireless motoring device
Time Frame	Assessed between baseline assessment and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	30	31
Mean (Standard Deviation) [percentage of days adherent to Wisepill]	60.0 (37.1)	28.2 (32.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.01
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-.287
	Confidence Interval	(2-Sided) 95%; -.507 to -.066
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Biological Measure of Substance Use
Description	Substance use measured with urinalysis.
Time Frame	Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	26	26
Positive	25 83.3%	23 74.2%
Negative	1 3.3%	3 9.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.28
	Comments	The overall omnibus test of the time by treatment interaction was p=.55. The estimate below is for post-treatment, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.95
	Confidence Interval	(2-Sided) 95%; -1.61 to 5.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Biological Measure of Substance Use
Description	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.
Time Frame	Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	26	25
Mean (Standard Deviation) [ng/mL]	484.2 (398.7)	414.7 (389.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.16
	Comments	The overall omnibus test of the time by treatment interaction was p=.38. The estimate below is for post-treatment, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	157
	Confidence Interval	(2-Sided) 95%; -67 to 382
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Changes in Self-reported Substance Use
Description	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.
Time Frame	Assessed between baseline assessment and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	26	26
moderate or high risk	23 76.7%	25 80.6%
low risk	3 10%	1 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.77
	Comments	The overall omnibus test of the time by treatment interaction was p=.90. The estimate below is for post-treatment, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	.25
	Confidence Interval	(2-Sided) 95%; -1.51 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Biological Measure of Substance Use
Description	Substance use measured with urinalysis.
Time Frame	Assessed at follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	27	29
Positive	20 66.7%	24 77.4%
Negative	7 23.3%	5 16.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.63
	Comments	The overall omnibus test of the time by treatment interaction was p=.55. The estimate below is for follow-up, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	.71
	Confidence Interval	(2-Sided) 95%; -2.24 to 3.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Biological Measure of Substance Use
Description	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.
Time Frame	Assessed at follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	25	29
Mean (Standard Deviation) [ng/mL]	538.4 (554.4)	386.1 (392.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.44
	Comments	The overall omnibus test of the time by treatment interaction was p=.38. The estimate below is for follow-up, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	84
	Confidence Interval	(2-Sided) 95%; -136 to 304
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Changes in Self-reported Substance Use
Description	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.
Time Frame	Assessed between baseline assessment and follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	27	29
moderate or high risk	24 80%	22 71%
low risk	3 10%	7 22.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.87
	Comments	The overall omnibus test of the time by treatment interaction was p=.90. The estimate below is for follow-up, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-.16
	Confidence Interval	(2-Sided) 95%; -1.85 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Intervention Acceptability
Description	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.
Time Frame	Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.
Measure Participants	26
Mean (Standard Deviation) [average score on a scale]	2.98 (.04)

9. Secondary Outcome

Title	Intervention Feasibility
Description	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.
Time Frame	Assessed at the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.
Measure Participants	26
Mean (Standard Deviation) [average score on a scale]	2.98 (.18)

10. Secondary Outcome

Title	Intervention Fidelity
Description	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).
Time Frame	Assessed between randomization and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.
Measure Participants	19
Measure Treatment session recordings	36
Mean (Standard Deviation) [Percentage fidelity to treatment]	91.7 (13.3)

11. Secondary Outcome

Title	Intervention Uptake
Description	Intervention participant attendance and retention (i.e., the mean number of intervention sessions attended by intervention participants)
Time Frame	Assessed between randomization and the acute outcome (approximately 12-weeks post-randomization/ post-intervention assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.
Measure Participants	30
Mean (Standard Deviation) [Sessions attended]	4.77 (1.96)

12. Other Pre-specified Outcome

Title	HIV Viral Load
Description	Percentage of patients with a suppressed viral load (<400 copies/ml)
Time Frame	Assessed at follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	27	29
Suppressed	16 53.3%	22 71%
Unsuppressed	11 36.7%	7 22.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.65
	Comments	The overall omnibus test of the time by treatment interaction was p=.89. The estimate below is for follow-up, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-.47
	Confidence Interval	(2-Sided) 95%; -2.49 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Other Pre-specified Outcome

Title	Changes in Self-reported Substance Use
Description	Changes in percent days used any substance measured by timeline follow-back
Time Frame	Assessed between baseline assessment and follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	27	29
Mean (Standard Deviation) [percentage of days used any substance]	30.7 (25.9)	25.1 (23.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.63
	Comments	The overall omnibus test of the time by treatment interaction was p=.66. The estimate below is for follow-up, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95%; -10.5 to 17.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Other Pre-specified Outcome

Title	Changes in Self-reported Substance Use
Description	Changes in number of drinks measured by timeline follow-back
Time Frame	Assessed between baseline assessment and follow-up (approximately 24-weeks post-randomization/ 6-month follow-up assessment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Project Khanya	ESOC
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.	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.
Measure Participants	27	29
Mean (Standard Deviation) [number of drinks on days drinking]	4.61 (3.29)	4.96 (4.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Project Khanya, ESOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.85
	Comments	The overall omnibus test of the time by treatment interaction was p=.94. The estimate below is for follow-up, comparing TAU to Khanya.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-.03
	Confidence Interval	(2-Sided) 95%; -.34 to .28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	While participants were active in the study (informed consent at baseline assessment until 6-month follow-up; approximately 6 months)
Arm/Group Title	Project Khanya		ESOC		Pre-Randomization
Arm/Group Description	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. Project Khanya: This treatment involves integrating a behavioral intervention for substance use with a behavioral intervention for adherence.		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.		Participants enrolled in the study at the baseline assessment, but who were never randomized (approximately 2 weeks post-baseline) and did not continue with the study.
All Cause Mortality
	Project Khanya		ESOC		Pre-Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)		0/31 (0%)		0/5 (0%)
Serious Adverse Events
	Project Khanya		ESOC		Pre-Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/30 (26.7%)		0/31 (0%)		1/5 (20%)
General disorders
Hospitalization	1/30 (3.3%)	2	0/31 (0%)	0	0/5 (0%)	0
Death	2/30 (6.7%)	2	0/31 (0%)	0	0/5 (0%)	0
Hospitalization	0/30 (0%)	0	0/31 (0%)	0	1/5 (20%)	1
Injury, poisoning and procedural complications
Hospitalization	1/30 (3.3%)	1	0/31 (0%)	0	0/5 (0%)	0
Pregnancy, puerperium and perinatal conditions
Hospitalization	1/30 (3.3%)	1	0/31 (0%)	0	0/5 (0%)	0
Psychiatric disorders
Hospitalization	1/30 (3.3%)	1	0/31 (0%)	0	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hospitalization	2/30 (6.7%)	2	0/31 (0%)	0	0/5 (0%)	0
Surgical and medical procedures
Hospitalization	1/30 (3.3%)	1	0/31 (0%)	0	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	Project Khanya		ESOC		Pre-Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/31 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.