Common Elements Treatment Approach HIV Alcohol Reduction Trial in Zambia

Study Overview
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Brief Summary
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This study, which is part of the Zambia Alabama HIV Alcohol Comorbidities Program funded by NIH-NIAAA, is designed to examine the efficacy of brief and in-depth cognitive behavioral therapy-based interventions to address, unhealthy alcohol use, comorbid mental health symptoms, and HIV treatment outcomes among people living with HIV in Zambia. A 3-arm trial will be conducted with participants randomized to a brief intervention alone, the brief intervention plus referral to Common Elements Treatment Approach (CETA), or standard of care (SOC).

Detailed Description
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People with HIV are a priority population for alcohol screening and treatment; however, they may be more likely to underreport their alcohol use and may respond less well to alcohol treatments due to untreated comorbidities. Psychological treatments for unhealthy alcohol use should ideally include components to address common mental health and other substance use comorbidities. However, few current treatments can treat both substance use and mental illness with a single protocol. Further, whether integrated treatment of unhealthy alcohol use and its comorbidities is more effective than alcohol-focused treatment alone needs to be established. There are psychological alcohol treatments that are consider brief interventions (BI), which are time limited and require fewer resources to implement. There are also more complex interventions that require multiple sessions with a provider and are more time and resource intensive; however, they may have more potential for short- and long-term effectiveness. In this study we will examine the efficacy of both a brief intervention (BI) alone and a more comprehensive and involving the BI followed by Common Elements Treatment Approach (CETA; www.cetaglobal.org) among adults with unhealthy alcohol use and HIV in urban Zambia. CETA is a transdiagnostic cognitive behavioral therapy-based intervention that can flexibly treat a range of conditions including substance use, depression, posttraumatic stress, and anxiety. Further, CETA can be delivered by professional and lay providers. There is already evidence that CETA can reduce alcohol use in the general population in Zambia. In pilot study, the BI plus CETA reduced alcohol use and mental health symptoms more at 6 months than the BI alone. Whether the BI is superior to standard of care (SOC), antiretroviral therapy adherence counseling, is not known. This study will build on existing knowledge by looking at longer-term effects (12 months) of the interventions, assess impact on HIV outcomes (adherence to antiretrovirals, retention in HIV care, viral suppression), and to understand whether the BI is superior to current SOC. In the study, we will also evaluate implementation factors related to delivery of the two interventions within public sector HIV clinics. Understanding how to implement interventions for unhealthy alcohol use and mental illness is a major priority in the field. We will have several groups of participants: 1 Adults with HIV and unhealthy alcohol use- this group will be enrolled and randomly assigned to one of three Arms (A, B or C) of the study. Arm A will receive alcohol brief intervention (BI), Arm B alcohol brief intervention (BI) plus referral to Common Elements Treatment Approach (CETA), or Arm C standard of care (SOC). The participants in Arm A will receive the single session alcohol brief intervention (BI). Participants in Arm B will also receive the BI and then be referred for CETA, which includes 6-12 sessions with a provider. The participants in Arm C will receive standard of care (SOC) only. All participants will be re-assessed at 6 and 12 months post-enrollment. Patients who participate will provide data on alcohol use, mental health and other substance use comorbidities, and HIV outcomes. Data will be generated through surveys and in some cases through laboratory tests (blood and urine). CETA will be provided by HIV peer counselors, a cadre of lay health worker that supports HIV care delivery at facilities in Zambia. 2 CETA counselors- this group will be enrolled and their competency to provide the intervention will be assessed through role plays. Further, they will be included in focus group discussions to understand experiences delivering CETA at HIV clinics. 3 Clinic staff- these individuals will be HIV care providers at the study clinics and they will be invited to focus group discussions so we can understand their perspectives on integration of interventions into their clinics. 4 Key informants- these are high-level policymakers and HIV and mental health/substance use policy makers and experts in Zambia who can guide us on understanding how to scale up study interventions should they be effective.

Official Title
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Common Elements Treatment Approach HIV Alcohol Reduction Trial in Zambia

Conditions
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HIV/AIDS, Alcohol-Related Disorders, Mental Illness

Intervention / Treatment
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* Behavioral: Alcohol Brief Intervention
* Behavioral: Common Elements Treatment Approach
* Behavioral: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Living with HIV Receiving HIV care at study site Hazardous alcohol use plus at least one mental health or other substance use comorbidity or moderate to severe alcohol use disorder regardless of comorbidity 6 months since initiation of Antiretroviral Treatment (ART) Suboptimal HIV care outcome based on at least 1 of the following occurences in the past year: Late (at least 14 days from scheduled) Antiretroviral Treatment (ART) drug pick up, HIV viral load (VL) above the limit of assay detection, or referral to enhanced adherence Exclusion Criteria: Plan to relocate out of Lusaka in next 6 months No access to a telephone Actively suicidal or alcohol intoxication and in need of immediate care Currently psychotic Participating in another interventional study that would interfere with participation

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: People meeting criteria will be assigned at random to one of 3 study arms.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A- Alcohol Brief Intervention<br>Following enrollment and randomization, participants will receive a single session of alcohol brief intervention (BI). Further, standard of care antiretroviral therapy (ART) adherence counseling will be provided as per local guidelines. | Behavioral: Alcohol Brief Intervention<br>* The alcohol brief intervention (BI) was based on CETA'S substance use module and was designed for one-on-one delivery. It is comprised of 6 elements (i.e. assessment, understanding impacts, exploring possibilities of change, goal setting, identifying reasons for alcohol use and skill building) including a 2-week alcohol timeline follow back assessment completed by provider. The alcohol brief intervention (BI) will be conducted by a trained counselor.<br>* Other names: BI;|
| Experimental: Arm B- Alcohol Brief Intervention plus Common Elements Treatment Approach<br>Following enrollment and randomization, participants will receive a single session of alcohol brief intervention (BI) and then will be referred to receive Common Elements Treatment Approach (CETA). Further, standard of care antiretroviral therapy (ART) adherence counseling will be provided as per local guidelines. For CETA, a specially trained counselor will contact the participant within 2 weeks of enrollment to arrange for CETA sessions, which occur approximately weekly. Participants will receive 6 to 12 sessions of CETA with the number of sessions based on symptoms and response to therapy. | Behavioral: Alcohol Brief Intervention<br>* The alcohol brief intervention (BI) was based on CETA'S substance use module and was designed for one-on-one delivery. It is comprised of 6 elements (i.e. assessment, understanding impacts, exploring possibilities of change, goal setting, identifying reasons for alcohol use and skill building) including a 2-week alcohol timeline follow back assessment completed by provider. The alcohol brief intervention (BI) will be conducted by a trained counselor.<br>* Other names: BI;Behavioral: Common Elements Treatment Approach<br>* CETA is a multisession cognitive behavioral therapy (CBT)-based model. CETA consists of elements: engagement, safety assessment, psychoeducation, substance use reduction, behavioral activation, cognitive coping, relaxation, exposure and problem solving. During a weekly clinic meeting, newly enrolled participants who are assigned to get CETA will be assigned to a specific counselor. The counsellor, together with their supervisor, will design an individualized treatment plan including type and order of Common Elements Treatment Approach (CETA) for each participant. The counsellor will contact participants by phone or home visit to schedule CETA session. CETA sessions will begin with standardized clinical monitoring form to track progress of treatment and each session will last 45-90 minutes.<br>* Other names: CETA;|
| Active Comparator: Arm C- Standard of Care<br>Following enrollment and randomization, participants will receive ART adherence counseling, which is the standard of care at the clinics. | Behavioral: Standard of Care<br>* Standard of Care (SOC) at HIV clinics in Zambia consist of Antiretroviral Treatment (ART) adherence counselling. All participants will receive Standard of Care (SOC), but for participants in Arm C it will be the only alcohol treatment. The ART adherence counseling includes brief unstructured discussion of substance use and mental health issues with a focus on issues that reduce adherence and retention issues. ART adherence counseling is delivered in a one-on-one format between patient and counsellor and it usually lasts 5-10 minutes.<br>* Other names: SOC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV Viral Load Suppression at 6 months | The study will focus on HIV viral load suppression with the definition being HIV RNA concentration below the sensitivity of the assay. In Zambia, it is possible that assays with slightly different HIV RNA sensitivity (for example 20, 40, and 60 copies per milliliter) may be used. Our definition for VLS will be having HIV RNA below the level of the least sensitive assay used during the study. We will estimate and compare risk differences with 95% CIs across the three study arms (i.e. 1=HIV VS and 0=no HIV VS). HIV viral suppression (VS) is the ultimate goal of ART and has individual and public health benefits. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alcohol Use from enrollment to 6 months | Alcohol use in the study will be measured by the Alcohol Use Disorders Identification Test (AUDIT). The minimum score on the Alcohol Use Disorders Identification Test (AUDIT) is 0 and maximum score on AUDIT is 40. For men, a score of 9 or greater indicates hazardous alcohol consumption. For women a score of 4 or greater indicates hazardous alcohol consumption. Higher AUDIT scores indicate unhealthy alcohol use. | 6 months | 
| Change in Alcohol Use from enrollment to 12 months | Alcohol use in the study will be measured by the Alcohol Use Disorders Identification Test (AUDIT). The minimum score on the Alcohol Use Disorders Identification Test (AUDIT) is 0 and maximum score on AUDIT is 40. For men, a score of 9 or greater indicates hazardous alcohol consumption. For women a score of 4 or greater indicates hazardous alcohol consumption. Higher AUDIT scores indicate unhealthy alcohol use. | 12 months | 
| Change in Alcohol Biomarker from enrollment to 6 months | The participant's blood level of phosphatidylethanol (PEth) will be analyzed in several ways. First describe the proportion with alcohol abstinence (PEth <8 ng/ml). Proportion with alcohol abstinence (PEth) level less than 20ng/ml indicate abstinence or light drinking. Second to describe proportion with unhealthy use (PEth>50 ng/ml). Proportion with alcohol abstinence (PEth) level of 20-200ng/ml indicate moderate level of drinking. Higher level of (PEth) indicate hazardous alcohol consumption. Ethl Glucuronide (EtG) will be analyzed to identify to identify patients with false reports of abstinence for exclusion from model. | 6 months | 
| Change in Alcohol Biomarker from enrollment to 12 months | The participant's blood level of phosphatidylethanol (PEth) will be analyzed in several ways. First describe the proportion with alcohol abstinence (PEth <8 ng/ml). Proportion with alcohol abstinence (PEth) level less than 20ng/ml indicate abstinence or light drinking. Second to describe proportion with unhealthy use (PEth>50 ng/ml). Proportion with alcohol abstinence (PEth) level of 20-200ng/ml indicate moderate level of drinking. Higher level of (PEth) indicate hazardous alcohol consumption. Ethl Glucuronide (EtG) will be analyzed to identify to identify patients with false reports of abstinence for exclusion from model. | 12 months | 
| Antiretroviral Treatment (ART) Medication Adherence from baseline to 6 months | Antiretroviral Treatment (ART) medication adherence will be assess based on the medication possession ratio (MPR). The medication possession ratio (MPR) metric used characterize engagement in HIV care and is a strong predictor of HIV viral suppression. These data include the date of each medication dispensation and the next scheduled drug pick-up date (based on the number of pills dispensed). MPR will be calculated from ART dispensation data that are extracted at enrollment, 6, and 12 months. | 6 months | 
| Antiretroviral Treatment (ART) Medication Adherence from enrollment to 12 months | Antiretroviral Treatment (ART) medication adherence will be assess based on the medication possession ratio (MPR). The medication possession ratio (MPR) metric used characterize engagement in HIV care and is a strong predictor of HIV viral suppression. These data include the date of each medication dispensation and the next scheduled drug pick-up date (based on the number of pills dispensed). MPR will be calculated from ART dispensation data that are extracted at enrollment, 6, and 12 months. | 12 months | 
| Change in HIV Viral Load from enrollment to 6 months | Defined as viral load <1,000 copies at 6 months. Testing will be done by a central lab and results will be returned to the clinic for entry into the patient's medical record so they can be used for clinical care. | 6 months | 
| Change in HIV Viral Load from enrollment to 12 months | Defined as viral load <1,000 copies at 12 months. Testing will be done by a central lab and results will be returned to the clinic for entry into the patient's medical record so they can be used for clinical care. | 12 months | 
| Retention in care change from enrollment to 6 months | Defined as being >28 days late for medication at 6 months calculated and compared across trial arms. | 6 months | 
| Retention in care change from enrollment to 12 months | Defined as being >28 days late for medication at 6 months calculated and compared across trial arms. | 12 months | 
| Changes in Mental Health and Substance Use from enrollment to 6 months | Changes in mental health, from enrollment to 6 months, based on the PHQ-9 for depression, HTQ for trauma, and GAD-7 for anxiety and changes in non-alcohol substance use based on ASSIST tool and a rapid point-of-care drug test | 6 months | 
| Changes in Mental Health and Substance Use from enrollment to 12 months | Changes in mental health, from enrollment to 12 months, based on the PHQ-9 for depression, HTQ for trauma, and GAD-7 for anxiety and changes in non-alcohol substance use based on ASSIST tool and a rapid point-of-care drug test | 12 months | 
| Change in Health Related Quality of Life (QoL) from enrollment to 6 months | Change in health-related Quality of Life (QoL) based on EQ-5D at enrollment and 6 months | 6 months | 
| Change in Health Related Quality of Life (QoL) from enrollment to 12 months | Change in health-related Quality of Life (QoL) based on EQ-5D at enrollment and 12 months | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Unhealthy Alcohol Use, Mental Illness, HIV care continuum, sub-Saharan Africa, Alcohol biomarkers, Implementation science