Acute Neural and Immune Effects of Alcohol in People Living With HIV Infection
Phase: NA
Conditions: HIV-1-infection, Alcohol Drinking
Sponsor: Brown University

Cover Page 
 
Title:   
 
Acute Neural and Immune Effects of Alcohol in People Living with HIV Infection 
NCT Number:   
NCT04050735 
Document Date:  
1/18/2023 
 
 
 

Study Aims: 
 
Aim 1. To investigate acute effects of alcohol on plasma biomarkers of microbial translocation and 
immune activation in PLWH (people living with HIV) and healthy controls using a controlled alcohol 
administration paradigm.  
Aim 2. To examine acute effects of alcohol on MRI correlates of neuroinflammation in PLWH and 
controls. 
Exploratory Aim 3: In the alcohol condition, PLWH will report higher subjective intoxication and exhibit 
greater alcohol-induced cognitive deficits than control participants. 
 
 
Study Design and Procedures: 
 
• 
Design and Overview: This study uses a between-subjects, placebo-controlled 2x2 design to test 
the acute effects of moderate alcohol consumption on brain, behavior, and immune function in 
people living with HIV and non-infected control participants. Participants in two groups (HIV 
seropositive, HIV seronegative) are randomized to receive either alcohol or placebo in this 2x2 
study design. The study involves screening, a baseline assessment (Visit 1), and one experimental 
session (Visit 2). Participants are compensated for their time and effort involved in participation.  
 
• 
Screening: Potential participants will be identified and recruited through collaboration with The 
Miriam Hospital Immunology Center or through online advertising. Potential participants will 
provide consent for screening. Those found to be eligible on a preliminary basis will be scheduled 
to attend Visit 1 at Brown University’s School of Public Health. 
 
• 
Visit 1: The research team will obtain informed consent for participation. In-depth assessment will 
determine eligibility to continue in the experimental portion of the study (Visit 2). Demographic 
information and social history will be collected. Participants will be interviewed about medical 
history, mental health, substance use, and other health-related behaviors. Breath alcohol 
concentration and other non-invasive physiological measures (e.g., blood pressure) will be 
collected. Urine samples will be collected and tested for drug metabolites and for pregnancy 
hormones (for women). Participants who meet all study criteria will be randomized to beverage 
condition and scheduled to return for Visit 2. Within groups formed on HIV status, participants will 
be randomly assigned to receive alcohol (.60 g/kg) or placebo beverage.  
 
• 
Visit 2: Participants will be instructed to fast overnight prior to Visit 2. Prior to experimental 
procedures, participants will complete measures of recent substance use, provide a breath alcohol 
sample and a urine sample for pregnancy testing (for women), and consume a standard snack. 
Blood samples will be taken prior to beverage administration and hourly for 3 hours afterward, to 
be used for testing primary biomarker outcomes. Participants will receive a beverage containing 
alcohol (.60 g/kg) or placebo. The alcohol dose is calculated to produce a peak blood alcohol level 
of .07 g/dl, which is considered a moderate level. Participants will be blinded to beverage contents. 
[Single-blinded administration (i.e., participant only) is permissible when double-blinded 
administration (i.e., participant and researcher) is not feasible due to COVID restrictions on 
laboratory personnel density.] Following beverage consumption, participants will complete tests of 
cognitive performance and subjective alcohol effects. When blood sample collection is finished, 
participants will be given a meal and non-alcoholic beverages. Then participants will complete a 1-
hour MRI scan of the brain at Brown’s MRI Research Facility. Participants will be released after 
data collection is complete and breath alcohol concentration is ≤ .039%. Participants will not be 
permitted to drive to or from Visit 2 and will be provided with transportation or reimbursement for 
transportation, according to their preferences. 
 
 
Potential Research Risks and Risk Mitigation: 
 
Potential Risks: 

 
1. General risks of mild-to-moderate alcohol intoxication. According to NIAAA guidelines,14 the target 
BAL of .07 g/dL typically is associated with mild-to-moderate impairment in orientation, speech, 
cognition, and coordination. 
2. Risks of alcohol consumption in PLWH. 
3. Risks of MRI scan.  
4. Psychological discomfort when answering questions about alcohol consumption habits, drug use, or 
psychiatric symptoms.  
5. Breach of confidentiality, including personal information about alcohol/drug use and HIV status. 
6. Physical risks associated with blood draw procedures: exposure to blood-borne viruses, infection at 
sampling site, pain or discomfort, hematoma, excessive bleeding, nerve damage, vasovagal reaction, 
or fainting.  
7. Risk of undue influence from compensation received for participation. 
8. Risk to a fetus from maternal alcohol consumption. 
9. Risk of distress from experimental manipulation (i.e., placebo-controlled alcohol administration). 
 
Protections against Risks: 
 
1. General risks of mild-to-moderate alcohol intoxication: At the recruitment and screening stage, risks 
to participants will be minimized through careful screening and selection of individuals who have past-
year experience with the study dose and who do not have medical or psychiatric conditions that would 
increase the likelihood of adverse reactions. During the beverage administration session, participants’ 
breath alcohol concentration will be assessed using a handheld digital sensor at baseline and at half-
hour intervals thereafter to ensure that levels follow the expected trajectory. Participants will be seated 
in a comfortable area where they can be monitored unobtrusively by research staff. To guard against 
injury, participants will be escorted to the restroom or during any other activity that involves ambulation. 
Participants will be monitored visually at regular intervals for signs of gross intoxication, including 
slurred speech, marked cognitive decline, or loss of psychomotor coordination. In the event of medical 
emergency, defined for the purpose of this study as breath alcohol >.15%, loss of consciousness, 
difficulty breathing, choking, chest pain, or severe disorientation, researchers will contact emergency 
medical services by calling 911. The PI or trained RA will be present or on call at all times when alcohol 
is administered. As part of the informed consent process, participants will be advised in plain language 
of the subjective and physiological effects that they may experience during the study. Once blood 
sample collection is complete, participants will be offered a standard meal and non-alcoholic beverages 
as refreshments. Participants will be instructed not to drive to experimental sessions, and any who do 
drive will be rescheduled for a later date. Participants will be provided with transportation to and from 
the experimental session at study expense. If participants choose to withdraw prior to study completion, 
they will be paid for their participation to that point, accompanied to a comfortable waiting area, and 
released once breath alcohol concentration ≤.039%. Transportation home will be provided at study 
expense regardless of study completion. A list of emergency personnel and contact phone numbers will 
be posted in the laboratory. In summary, participants who receive alcohol are likely to experience some 
alcohol-related impairment, and study procedures are designed to minimize any negative 
consequences of this impairment. 
 
2. Risks of alcohol consumption in PLWH: As described above, Dr. Tashima will assess all participants 
for suitability for study participation. Potential concerns about acute alcohol effects in PLWH and 
alcohol-antiretroviral (ART) drug interactions are addressed below. 
2A. Dose tolerability. Tolerability of the .60 g/kg alcohol dose is supported by several prior 
studies that have administered higher doses to PLWH without serious adverse events. One 
study administered an alcohol dose of 1.0 g/kg to 15 PLWH, resulting in peak BAL ³ .11 g/dL.15 
Another administered 0.70 g/kg of alcohol to 24 PLWH to produce peak BAL around 0.05 g/dL.16 
A placebo-controlled trial with 141 HIV-infected men administered alcohol in a dose to effect 
peak BAL of .086; Dr. Monti (Mentor) was a collaborator on this study.17 None of these studies 
reported serious adverse events in PLWH who were selected using criteria comparable to the 
current proposal. As specified in Eligibility Criteria, only individuals who report recent alcohol 
self-administration equal to the study dose will be eligible for participation, reducing the 
likelihood of adverse events.  

2B. Risk of alcohol-antiretroviral drug interactions. Research on ART-alcohol interactions is 
limited. Current NIH Guidelines for Antiretroviral Use in HIV-1-Infected Adults and Adolescents do 
not state that moderate alcohol use by ART recipients is contraindicated.5 Rather, research 
supports advising HIV patients to adhere to their prescribed ART regimens when choosing to 
drink alcohol.18,19 One study found no evidence of alcohol-ART pharmacokinetic interaction, and 
co-administration of alcohol with ART did not significantly increase subjective intoxication or 
cognitive deficits.15,20 In a primate model, Molina et al. (2014) found no evidence that chronic 
binge alcohol increased the toxicity or altered the effectiveness of tenofovir or emtricitabine.18 
Moreover, a prospective cohort study found that PLWH on ART who drank moderately did not 
exhibit more liver fibrosis than non-drinking PLWH, regardless of ART type. Under no 
circumstances will an individual’s ART regimen be changed to allow participation. The PI will 
consult Dr. Karen Tashima (Collaborator), research publications, and NIH Guidelines on an 
ongoing basis for newly reported alcohol-ART interactions. In summary, alcohol-antiretroviral 
drug interactions are considered very unlikely. 
 
3. MRI risks: MRI has no known side effects and does not involve radiation. However, there are several 
contraindications for MRI scan. The first is metallic materials/implants within the body, such as 
aneurysm clip, bullet or shrapnel fragment, ear implant, certain prosthetic devices, heart pacemaker, or 
artificial heart valve. Participants will be thoroughly screened to prevent admission of individuals with 
these contraindications to the MRI suite. The second contraindication is pregnancy, as risks to the fetus 
are unknown. Pregnancy tests will be administered to all female participants at the baseline 
assessment and again on the day of MRI scanning, prior to starting experimental procedures. Third, 
there is risk of subjective discomfort from being in a small space or from noise emitted by the scanner. 
Participants will be given a call button to hold during the MRI so that they can communicate distress to 
the MRI technician and research staff, and procedures can be discontinued if indicated. Participants will 
be required to wear earplugs to reduce exposure to noise from the scanner. Serious risks of MRI are 
not likely given these safety precautions, and the subjective discomforts that may occur (e.g., 
discomfort in an enclosed space) are likely to be small in magnitude and transient in nature.  
 
4. Psychological discomfort associated with assessment: Participants will be advised during the 
informed consent process that they may choose not to answer any particular question, that their verbal 
and written responses are confidential, and that they are free to withdraw from the study at any time. 
Medical screening, questionnaire completion, and laboratory procedures will be performed in private 
rooms reserved for these purposes. Given these precautions, it is not likely that severe psychological 
distress will occur. 
 
5. Loss of confidentiality: Several steps will be taken to protect against loss of confidentiality. All data 
will be collected and stored using technology that employs the industry standard for security. Data will 
be stored in de-identified, password-protected files on Brown University’s secure servers. Participant 
data and samples will be identified using a unique, randomly generated ID code. Participants’ personal 
identifying information will be kept in a separate location from their response data. At the conclusion of 
the study, the file that contains links of personal identifiers with unique study IDs will be destroyed by 
the study PI. The COBRE CLC Data Analyst and Data Systems Management Coordinator will collate 
and store data on the secure server, using appropriate measures for data protection. All data collected 
via computer will be stored on Brown University’s encrypted, secure servers and accessed through 
password-protected computers only by primary research staff. Biological samples will be identified with 
the participant’s study ID and will not be associated with personal identifying information or clinical 
medical records. With these precautions, loss of confidentiality is considered very unlikely; however, 
participants will be informed of this risk at the time they provide consent.  
 
6. Risks from blood draw procedures: During the informed consent process, participants will be advised 
of the necessity of obtaining repeated blood samples during the experimental session. Screening will 
exclude individuals who report psychological discomfort caused by blood draw or the sight of blood, or 
who report history of adverse reaction to standard blood draw procedures. Collection will utilize an IV 
catheter set to avoid repeated needle sticks. The total volume of blood to be collected is modest. Blood 
draw procedures will follow World Health Organization guidelines for safe and well-tolerated procedures 
to minimize risk of infection or other complications.8 The CLC Nurse Practitioner will collect the blood 
samples. Risk reduction strategies are to use sterile, single-use implements; surface disinfectant; 

proper hand hygiene; application of 70% isopropyl alcohol to the blood draw site; minimal vein probing; 
application of pressure after drawing blood; an IV catheter set; and non-latex, vinyl gloves. Blood draw 
by a licensed professional using these risk reduction methods makes the occurrence of negative 
outcomes very unlikely. 
 
7. Risk of undue influence from monetary compensation: This risk is low, as the total amount of 
compensation is modest. The hourly compensation rate for the study sessions translates to 
approximately $17-25/hour, which is consistent with rates offered by similar studies in the Brown 
University area. This rate is somewhat higher than the living wage (approximately $11/hr; 
livingwage.mit.edu) for Providence County, RI, to account for inconvenience and/or discomfort 
potentially associated with study procedures. 
 
8. Risk to fetus from maternal alcohol consumption: Due to the harmful effects of alcohol on fetal 
development, all participating women will be required to take a pregnancy test at the beginning of every 
study session. Females will be excluded if they express unwillingness to use effective birth control 
throughout the study if sexually active with a male partner. Female subjects who test positive for 
pregnancy will be informed that they have had a positive test result and are not eligible to participate in 
the study. They will be informed that it is possible to have a false positive result and will be encouraged 
to follow up with a medical provider of their choosing. Subjects who are breastfeeding or who intend to 
become pregnant during the course of the study will be excluded. These precautions make it very 
unlikely that a fetus will be exposed to alcohol from maternal consumption in the course of this study. 
 
9. Risk of distress from experimental manipulation: All participants will undergo debriefing upon 
completion of the blinded alcohol administration protocol using the attached Debriefing Form. 
Participants will be given the opportunity to ask questions about the experiment. Each participant will be 
reminded that his or her copy of the informed consent document contains contact information for the PI 
(Dr. Monnig) and Brown University IRB, and will be encouraged to contact these entities if concerns 
arise in the future. 
 
 
Statistical Analysis Plan:  
 
Aim 1. To investigate acute effects of alcohol on plasma biomarkers of microbial translocation and immune 
activation in PLWH and healthy controls using a controlled alcohol administration paradigm.  
 
Aim 1 Analytic Plan: Linear mixed models will be used to analyze the effects of the factors of interest on 
plasma biomarkers. Models will include random effects for intercept and/or slope where indicated. 
Different covariance structures to be tested for best fit include unstructured, compound symmetric, and 
autoregressive.  
 
Aim 2. To examine acute effects of alcohol on MRI correlates of neuroinflammation in PLWH and controls. 
 
Aim 2 Analytic Plan: Analysis of variance (ANOVA) will test the main effect of beverage condition on 
MRS outcomes (Hypothesis 2A) and DWI (Hypothesis 2C) outcomes. Hypotheses 2B and 2D, 
predicting differential changes in MRS and DWI outcomes in PLWH in the alcohol condition, will be 
assessed in the interaction of beverage condition by HIV status. 
 
Exploratory Aim 3: In the alcohol condition, PLWH will report higher subjective intoxication and exhibit greater  
alcohol-induced cognitive deficits than control participants. 
 
Aim 3 Analytic Plan: ANOVA will be used to test main effects of HIV status, alcohol condition, and their 
interaction on cognitive performance and subjective intoxication.