Improving HIV and Alcohol-Related Outcomes Among HIV+ Persons in Clinic Settings
Phase: NA
Conditions: HIV, Alcohol Use, Medication Adherence
Sponsor: Hunter College of City University of New York

 
 
 
 
 
PLUS: Full Trial Protocol 
Improving HIV and Alcohol-Related Outcomes among HIV+ Persons in Clinic Settings 
NCT02390908 
 
 
Funded by the National Institute on Alcohol Abuse and Alcoholism 
CET: RO1AA022302 
PI: Tyrel J. Starks, PhD, June 2018 to May 2020 
PI: Jeffrey T. Parsons, PhD, August 2013 to June 2018 
 
Hunter College of the City University of New York (CUNY) 
 
In Collaboration with: 
Spencer Cox Center for Health  
Mt. Sinai St. Luke’s and Mt. Sinai Roosevelt Hospitals 
Research Foundation for Mental Hygiene 
 
Correspondence concerning this protocol should be addressed to: Tyrel J. Starks, Department of 
Psychology, Hunter College of the City University of New York, 695 Park Ave., New York, NY 
10065. Fax: 212-206-7994. Email: tstarks@hunter.cuny.edu  
 
Document Approved: 11.12.2020 
 
 
 
 
 

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ADDRESS AND STUDY SITES 
 
 
Hunter College, City University of New York (CUNY) 
142 West 36th Street, 9th Floor 
New York, NY 10018 
212-206-7919 
 
SITE 1: 
West 17th Street Clinic 
230 West 17th Street between 7th and 8th Avenue 
6th, 7th and 8th Floors 
New York, NY 10011 
212-523-6500 
 
SITE 2: 
Mount Sinai Comprehensive Health Program - Downtown  
275 7th Avenue – 12th Floor 
New York NY 10011 
 
SITE 3: 
Morningside Clinic 
St. Luke’s Hospital 
390 West 114th Street, 3rd Floor 
New York, NY 10025 
212-523-6500 
 
No-Treatment Control Group obtained at: 
Samuels Clinic 
Roosevelt Hospital 
1000 10th Avenue, Suite 2T 
New York, NY 10019 
212-523-6500 
 
 

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LIST OF ABBREVIATIONS 
 
ART 
 
 
Antiretroviral Therapy 
AUDIT  
 
Alcohol Use Disorders Identification Test 
BL 
 
 
Baseline 
BSI 
 
 
Brief Symptom Inventory 
CASI  
 
Computer Assisted Self Interview 
CBT 
 
 
Cognitive Behavioral Therapy 
CBST  
 
Cognitive Behavioral Coping-Skills Training 
CET 
 
 
Comparative Effectiveness Trial 
DAST  
 
Drug Abuse Screening Test 
EMR 
 
 
Electronic Medical Record 
E-TAU  
 
Enhanced Treatment as Usual 
FU 
 
 
Month Follow-Up 
ICD 
 
 
International Classification of Diseases 
IP 
 
 
Immediate Post-Test Assessment 
IRB 
 
 
Institutional Review Board 
MI 
 
 
Motivational Interviewing 
MITI 
 
 
Motivational Interviewing Treatment Integrity Coding System 
NIAAA 
 
National Institute on Alcohol Abuse and Alcoholism 
NIH 
 
 
National Institute of Health 
PI 
 
 
Principal Investigator 
PID 
 
 
Participant Identification Number 
PLUS  
 
Positive Living through Understanding and Support 
QA 
 
 
Quality Assurance 
RA 
 
 
Research Assistant 
TAU 
 
 
Treatment as Usual 
VAS 
 
 
Visual Analogue Scale 
VL 
 
 
Viral Load 
 
 
 
 

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PLANNED STUDY DESIGN 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Evaluation in Person or 
by Telephone using Screening* 
If eligible, schedule 
Baseline* Assessment 
Baseline Visit** (N = 240) 
Informed Consent,* CASI, and blood 
drawn 
EMR Data 
Immediate Delivery (n=120) 
PLUS 8-12 weeks + E-TAU 
Session 1, 2, 3, 4, 5, 6 
Waitlist Delivery (n=120) 
E-TAU Wait-List Condition 
Control EMR 
(n=120) 
TAU alone 
3-Month Post-Test Assessment  
6-Month Post-Test Assessment 
Optional booster session 
9-Month Post-Test Assessment 
Optional booster session  
12-Month Post-Test Assessment 
Optional booster session  
15-Month Post-Test Assessment 
Optional booster session 
18-Month Post-Test Assessment 
Optional booster session 
6-Month Assessment  
9-Month Assessment 
12-Month Assessment + PLUS  
8-12 weeks Session 1, 2, 3, 4, 5, 6 
 15-Month Post-Test Assessment 
Optional booster session 
18-Month Post-Test Assessment 
Optional booster session 
*Screening, 
consent, and 
baseline may 
happen in separate 
visits or in 
combination 
**Upon completion 
of baseline 
participants are 
counted as 
ENROLLED 
 
3-Month Assessment  

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STUDY OBJECTIVES 
Our goals were to better understand alcohol-related outcomes among HIV-positive persons over 
the lifespan and to implement a multisite comparative effectiveness trial (CET) in real-world 
clinical settings with three intensities of treatment to test their relative effectiveness in improving 
ART-adherence and alcohol-related outcomes among HIV-positive individuals who drink 
alcohol at harmful or hazardous levels. We aimed to achieve the following four Specific Aims: 
Aim 1: Adapt the PLUS intervention for delivery in HIV clinic settings by mental health 
providers, and incorporate booster sessions designed to sustain longer-term effects. We 
aimed to conduct formative research, and utilize our findings as well as capitalize on existing 
systems and approaches utilized by SCCH (e.g., text messaging) to adapt PLUS for delivery in 
clinic settings as well as to develop booster sessions. 
Aim 2: Test the effectiveness of the PLUS intervention delivered in a consortium of HIV 
clinics in New York City using a multisite CET with three intensities of treatment. Our 
primary goal was to test the PLUS intervention—an efficacious, theory-based intervention that 
integrates MI and CBST—versus an eTAU condition and TAU alone in reducing alcohol use and 
improving ART adherence, viral, and immunologic outcomes among HIV+ hazardous drinkers. 
Aim 3: Assess the cost-effectiveness of PLUS. If effective, we aimed to conduct analyses to 
assess the cost-effectiveness of PLUS in treating HIV+ hazardous drinkers compared to eTAU 
and TAU alone as estimated over 5- and 10-year windows. 
Aim 4: Collect and analyze retrospective cohort data and prospective natural history data, 
via Electronic Medical Records (EMR) at the SCCH clinics. We aimed to conduct 
retrospective cohort analyses to compare virologic, immunologic, medical outcomes, and 
adherence to medical appointments/engagement in care between those who do (n = 1505) and do 
not (n = 3692) meet diagnostic criteria for alcohol abuse/dependence. We aimed to use the third 
SCCH clinic (which will not receive any intervention) as a natural history comparison group, and 
conduct prospective analyses of data to better understand the natural history of the intersection 
between problematic alcohol use and HIV medication adherence and HIV health outcomes. Of 
particular focus were analyses of potential differences by age, race/ethnicity, gender, sexual 
identity, viral hepatitis co-infection, years living with HIV, and years on ART. 
 
 

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Trial Design  
This study utilized a CET design to evaluate the effectiveness of the PLUS intervention 
components against a waitlist condition, and for VL and CD4, against a No-Treatment control 
group. Four sites were distributed across three study conditions in a quasi-experimental design. 
Two sites (Sites 1 and 2) implemented immediate treatment (Condition 1). Immediately after 
baseline, participants were offered the PLUS intervention. Participants then completed follow-up 
assessments at 3, 6, 9, 12, 15 and 18 months post-baseline. Site 3 implemented both the waitlist 
condition (Condition 2) from March 26, 2015 to October 31, 2016, and an immediate condition. 
Due to challenges in participant accrual, this site shifted to enrolling participants in the 
immediate intervention condition from November 1, 2016 through the end of the study. 
Participants in the waitlist condition received the intervention following completion of their 12-
month follow-up. Site 4 is the no-Treatment Control EMR Group. 
METHODS: Participants, Interventions and outcomes  
Inclusion Criteria 
• 18 years of age or older 
• HIV-positive 
• Currently receiving ART 
• Current VL ˃200 copies/ml 
• Report drinking at hazardous levels, operationalized as exceeding 14 standard drinks per 
week for men or exceeding 7 standard drinks per week for women, as per NIAAA 
guidelines. In a later amendment, criteria were expanded to also include reported use of 
illicit drugs exclusive of marijuana or illicit use of prescription opioids within the past 3 
months. 
• Must be a current patient at the clinic with current lab results 
Exclusion Criteria 
• Effectiveness trials should enroll participants that reflect the population for which the 
treatment is intended. Thus, we are keeping exclusion criteria to a minimum and 
imposing few eligibility criteria to identify our target clinical population. 
• Given that the PLUS manual with guided step-by-step instructions, questions, and probes, 
as well as various modules and hand-outs for participants are all in English, study 
candidates will need to be able to communicate effectively in English. 

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• Any thought disorder (e.g., psychosis, schizophrenia, bipolar, having severe symptoms of 
psychological disorder) that would impair the individual’s ability to provide informed 
consent or interfere with the study procedure.    
*** NOTE: Co-morbidities such as mental health problems, i.e., depression and anxiety 
disorder, and drug use are NOT considered exclusion criteria. Additionally, current or 
previous participation in behavioral or neurocognitive studies or interventions is NOT 
considered an exclusion criterion.  
• Intoxication or under the influence of alcohol or other substances at the time of consent 
that would impair the individual’s ability to provide informed consent or interfere with 
the study procedure. 
 
INTERVENTION PROCEDURES 
The six-session intervention is based on the PLUS (Positive Living through Understanding and 
Support) Clinical Protocol Manual. PLUS is an efficacious, theory-based intervention that 
utilizes motivational interviewing and cognitive behavioral skills training to reduce alcohol use 
and improve medication adherence. The participants were informed that the sessions would 
focus on alcohol use, other drug use and medication adherence. Sessions were delivered by a 
study therapist (psychologists, social workers and psychiatrists) employed at the clinics.     
Six Sessions of PLUS 
Session 1: Guidance on Participant Engagement in MI 
In Session 1, the therapist spends some time talking about the participant’s perception of their 
behaviors (drinking, substance use and medication adherence) and what types of changes they 
would like to make. During these first sessions, the therapist focuses on a target behavior and 
offers them feedback from the assessment instruments they completed at baseline. In an MI-
consistent style, the therapist proceeds with strategies such as using open questions and 
reflections to elicit and evoke participant’s readiness for change, and may move towards the 
planning phase collaborating on a change plan.  
Session 2: Overview of Functional Analysis Session 
The second session began with re-engagement briefly summarizing the last session’s major 
themes on alcohol, substance use and adherence, highlighting any goals or plans that were 
discussed. The therapist explores recent episodes of all relevant target behaviors – drinking, 

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using drugs, and missing doses of HIV medication in order to gain a comprehensive 
understanding of the common contexts of the participant’s risk behaviors. Although in this 
session the therapist begins using CBST techniques, the goal was to continue to communicate 
with the participant in an MI consistent fashion, using “OARS” (Open Questions, Affirmations, 
Reflections and Summaries) reflective listening skills. As these patterns become more clear, the 
therapist organizes them into a functional analysis, which summarizes the chain (or sequence) of 
events, behaviors, and consequences typically involved in the target behaviors. The therapist can 
then examine patterns across these chains to create a case conceptualization. Next step involves 
orienting the participant to the idea that chains can be disrupted. The creation of this functional 
analysis provides a starting point for discussing the rationale for CBT intervention and also for 
planning the specific CBST skills that a particular participant might focus on.  
Sessions 3-5: Overview of Session Protocol for CBST Sessions 
Each of the three CBST sessions follows a similar protocol, although a different module/s may 
be covered in each session. Although modules are general guidelines for delivering skills, 
content covered with the participant should be specific to the participant’s needs. The therapist 
should try to complete at least two modules for each target behavior (substance use / medication 
adherence). More than one module may be presented to the participant during a single session, 
but it is important that the participant doesn’t become overwhelmed by information. With 
permission, teach coping skills, conduct in-session exercise, and assign practice exercise.  
Session 6: Overview of Relapse Prevention Protocol 
Initial step of this session is to briefly review the goals previously identified in the change plan. 
This summary should acknowledge ongoing discrepancy between current and desired status; 
however, it should also incorporate an emphasis on progress made during treatment. If the 
participant is in action or maintenance phase, the therapist needs to assess the participant’s 
interest and willingness to discuss a relapse prevention plan. The therapist also needs to 
collaborate with the participant to develop an emergency plan on how they might cope with a 
high risk situation and what they would do should a slip or relapse occur.  
Booster Session: 
The purpose of the optional booster session was to ‘check in’ with the participant on how they 
are doing with their drinking, substance use and HIV medication adherence, and remind them of 
when their next booster is (except for when this is the final booster session). At the end of the 

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session, summarize the main points affirming any efforts the participant has made to proceed 
towards their goals. Briefly recap any plans made during the session, including any plans to 
access referrals.  
Timeline 
The PLUS intervention was adapted from an original eight session intervention to six sessions 
based on feedback from mental health staff at the sites. c. Research staff will keep track of 
participant’s attendance during PLUS intervention period via the tracking log. Booster sessions 
will also be scheduled and conducted but will not be required for treatment exposure to the 
PLUS intervention.  
Enrollment in Immediate and Waitlist control conditions 
Potential participants in the immediate and waitlist control conditions were identified through a 
prescreening review of EMR, which provided study staff members with lists of patients with 
scheduled clinic visits who had one or more detectable viral load within the past year. Study staff 
approached these patients during clinic visits to introduce PLUS and invited them to participate 
in screening. Participants provided verbal consent for screening and provided written informed 
consent if they were eligible and interested in enrolling. They also granted permission for the 
study team to abstract their EMR data for study screening and enrollment purposes.  
Once consent to use the EMR was granted, eligibility criteria were verified for ART regimen and 
viral load. Participant self-report was used to determine alcohol and substance use criteria on the 
screening questionnaire. Eligible participants who enrolled in the study were scheduled for a 
baseline visit, which could take place the same day post-screening or be scheduled within the 
ensuing month. The full protocol was approved by the institutional review boards at Hunter 
College and Mt Sinai. 
Therapist Training 
All therapists involved in the PLUS intervention were trained on Motivational 
Interviewing (MI), Cognitive Behavioral Skills Training (CBST), and the PLUS Clinical 
Manual. MI and CBST trainings were provided by the Center for HIV Educational Studies and 
Training (CHEST). After trainings, therapists held four mock-sessions with a mock participant. 
All MI mock sessions were coded via the Motivational Interviewing Treatment Integrity (MITI) 
system and were reviewed for fidelity with CBST. Therapists were given feedback from trainers 

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and were asked to repeat session based on feedback to reach competency in intervention as 
needed.  
Intervention Monitoring and Quality Control 
Standardized rating systems (MITI Coding with a CBST checklist) were used to evaluate 
the competency of study therapists prior to rollout of the full trial. Once the trial began, we 
monitored the implementation and select 25% of taped sessions to assess fidelity to protocol.  
MEASURES 
Primary Outcome Measures 
• Biological Marker of HIV-Related Health Outcomes  
o Viral load and CD4 extracted from EMR 
• Alcohol Use 
o Alcohol Use Disorders Identification Test (AUDIT) 
o Hazardous Drinking 
• Medication Adherence 
o Visual Analog Scale (VAS) for Medication Adherence 
Secondary Outcome Measures 
• Substance Use 
o Drug Abuse Screening Test (DAST) 
Other Self-Reported Measures 
• Demographics 
• Brief Symptom Inventory-18 (BSI-18) 
• Self-Efficacy VAS for Alcohol, Drugs, Adherence, Sex Risk, and Doctor’s Visits 
• Patient Satisfaction 
o Participant Experience of Motivational Interviewing (CEMI) Scale 
o Patient’s Experience with the Provider 
Data Collection 
All baseline and follow-up assessments are administered at the study sites. Baseline data 
collection was completed within the same day, and no later than 7 days after the screener is 
completed. All follow-up data collections (3M, 6M, 9M, 12M, 15M, and 18M) could be 
collected up to 14 days prior/post to their follow-up target date and up to 28 days post their 
follow-up target date.  

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Compensation 
To compensate participants for their time and efforts in taking part in the PLUS trial, gift cards 
and metro cards were given out at each assessment and therapy visit, respectively, in two 
different denominations for participant compensation: 
$25 Gift cards- which will be dispersed during study assessments (BL, 3M, 6M, 9M, 12M, 15M, 
and 18M) 
$10 Metro cards- which will be dispersed during therapy visits (Sessions 1-6) 
Throughout the course of the PLUS trial, a study participant may receive $235 for their 
participation.   
Selection of No Treatment control patients 
The EMRs of randomly selected patients who belonged to the TAU site and were not 
enrolled in the PLUS trial were matched on key patient characteristics for comparisons with 
EMRs of patients in the PLUS intervention and Waitlist control conditions. This matched cohort 
of patients received care at a fourth clinic that did not receive any intervention (i.e., PLUS or 
eTAU) and was considered as a natural history comparison group. We generated a pool of 
patient records from which to randomly select the TAU matched cohort of patients (n = 120). We 
included patient records of patients with an HIV diagnosis who had at least 1 primary care visit 
at the TAU clinic, received ART, and had a viral load (VL) >200 copies/mL during the PLUS 
enrollment period from March 26, 2015 to March 16, 2017. EMRs of 20 patients who were 
enrolled in PLUS and possibly transferred to receive HIV care at the TAU clinic during the study 
period were excluded. Additionally, records of 9 patients with only one primary care visit and no 
follow-up visits during the study period were excluded from the pool of patient records.  
Case control matching using the pool of patients meeting the criteria described above 
allowed us to randomly select the TAU cohort of 120 patients while matching as closely as 
possible to patients enrolled in the trial on key variables: age group (with ranges 18-29, 30-39, 
40-49, and 50 or older), racial and ethnic identity (Black, Hispanic/Latinx, White, Asian/Pacific 
Island, Other/Multiracial), and gender (recorded as male or female). Additionally, we matched 
on indicators of substance misuse based on EMRs of trial participants using documentation of 
substance use problems or ICD-10 diagnostic codes, such as documentation of alcohol abuse or 
dependence, having had a substance use diagnosis, or any indication of substance misuse during 
the study period. EMRs were then extracted for the TAU cohort of patients similar to the records 

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for the trial participants. A de-identified dataset was generated linking all patient EMRs to an 
unique study ID number with the following variables: demographic variables, HIV diagnosis, 
HIV clinical outcomes, ARV regimen, ICD-10 diagnoses of AIDS defining illness, substance use 
disorders, psychiatric disorders, non-AIDS defining infections (bacterial pneumonia, cellulitis, 
sepsis), cardiovascular, gastrointestinal, liver, kidney, pulmonary, endocrine, immune, and 
oncologic diseases, as well as sexually transmitted infections. In addition, records about services 
received and type of outpatient clinic visits were extracted, such as whether the visit was an HIV 
primary care visit, a specialty or non-HIV primary care visit type (dentist, OB/GYN, 
hematology), mental health visit, and substance use visit. 
Data Analysis Plan  
To assess the effectiveness of our randomization procedure, we used chi-square tests and 
ANOVAs to investigate the equivalence of possible cofounders across each of the PLUS-
enrolled four site/conditions at baseline. Specifically, we examined proportional differences 
across demographic characteristics (race and ethnicity, sexual and gender identity, and 
education), and mean differences across age and baseline outcome values (alcohol severity, drug 
use severity, medication adherence, viral load, and CD4). Where cell sizes were too small (n < 5) 
to permit chi-square tests, we utilized a Fisher’s exact test, at p <.05. The matching of the No 
Treatment control group (N = 120) was assessed by bivariate comparisons with the entire PLUS-
enrolled sample (N = 174) on the available variables of age, race and ethnicity, and gender.  
 We also conducted analyses to test for the presence of differential attrition between 
conditions and sites where appropriate. First, we conducted chi-square analyses to test for 
differential attrition by site and study arm at each follow-up. We also tested for differential 
attrition at each follow-up across site, as well as several demographic characteristics (race and 
ethnicity, sexual and gender identity, and education). Finally, we conducted a series of point-
biserial correlations to examine attrition at each wave by age and baseline outcome values 
(alcohol severity, drug use severity, medication adherence, viral load, and CD4).  
Outcome analyses were conducted using piece-wise longitudinal growth curve models, 
adjusting for baseline scores on the corresponding outcome and, for the models predicting 
medication adherence, AUDIT, and DAST, we also adjusted for gender identity and sexual 
orientation, whereas for the models predicting viral load and CD4 we adjusted for gender (male, 
female) as sexual identity was not indicated in the EMR records for the matched cohort. For the 

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DAST model, DAST was treated as a count variable having a negative binomial distribution. The 
latent intercept represented the initial 3-month follow-up time point. Slope 1 quantified linear 
change across the 3-, 6-, 9- and 12-month follow-ups. Where possible for outcomes variables 
extracted from EMR (i.e., CD4 count and viral load), Slope 2 quantified changes in trajectory at 
the 15- and 18-month follow-up corresponding to the point at which the waitlist control 
condition received the intervention. The fixed effect of clinic and condition was entered as a 4-
category predictor that was dummy-coded. For viral load and CD4 models – where data were 
taken from EMR records – the EMR cohort control participants were included as an additional 
subgroup and served as the referent category.  
All models were estimated using full-information maximum likelihood estimation in 
MPlus Version 8.0. Good model fit was assumed when the χ2/df ratio was 3 or less, root-mean 
square error of approximation (RMSEA) ≤ 0.05, Tucker-Lewis fit index (TLI) > 0.95, and 
comparative fit index (CFI) > 0.95. 
Data Monitoring  
The study protocols are approved by the research ethics board of the principal 
investigator’s academic institution and Mt Sinai, and are registered with clinicaltrials.gov 
(NCT02390908). 
 
DECLARATIONS:  
Availability of data and material: Not applicable as this manuscript contains no data.  
Competing interests: The authors declare that they have no competing interests.  
Acknowledgements: We acknowledge our partnership with collaborators Dr. Martha Sparks, 
Chris Ferraris, and Dr. Ana Ventuneac, as well as the contributions of the PLUS Project Team, 
particularly Dr. Sitaji Gurung, Dr. Juline Koken, Laurie Spacek, Doug Keeler, Elizabeth 
Savarese, Juan Castiblanco, Theresa Navalta, Joseph Carter, Evie Arroyo, Chloe Mirzayi, Tina 
Koo, Ruben Jimenez, Scott Jones, Simone Skeen, and our research coordinators, Sylviah Nyamu 
and Kelly Reilly. We also thank our staff, recruiters, interns, and our participants who 
volunteered their time. 
Funding: This study was supported by a grant from the U.S. National Institute for Alcohol 
Abuse (R01 AA022302, PI – Starks).