Acute Neural and Immune Effects of Alcohol in People Living With HIV Infection

This study will examine whether moderate alcohol use in the context of HIV infection exacerbates inflammatory signaling in the immune system and brain. The study will recruit healthy individuals and people living with HIV infection who are otherwise in good health to participate. Participants will complete an experimental protocol that involves controlled alcohol administration and magnetic resonance imaging (MRI). Primary outcomes are plasma biomarkers of inflammation and MRI markers correlated with neuroinflammation. Results will advance understanding of the effects of alcohol use in people living with HIV infection.

Study Overview

• Status: Completed
• Conditions: Alcohol Drinking; HIV-1-infection
• Intervention / Treatment: Other: Alcohol, ethyl, moderate dose; Other: Placebo

Detailed Description

A sample of 56 participants, to include equal numbers of people living with HIV and uninfected controls, will be recruited to complete the experimental protocol. Participants will be randomized to one of the two beverage conditions (0.60 g/kg alcohol beverage, 0.00 g/kg placebo beverage). Blood samples will be collected at baseline (prior to beverage administration) and for three hours afterward. Cognitive performance and subjective intoxication will be assessed using standardized measures. MRI scans will be collected 4-5 hours after beverage consumption to capture neurobiological outcomes on the descending limb of blood alcohol.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Brown University and The Miriam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

General Inclusion Criteria:

1. 21-60 years old;
2. Able to speak and read English at least at 8th grade level;
3. Alcohol use ≥.60 g/kg at least once in past year. In standard drinks, this amount translates to 1.9-3.0 drinks for an average-weight female and 2.4-3.9 drinks for an average-weight male.
4. Body mass index of 18.5-34.9 kg/m2;
5. Lab tests obtained in past year showing no evidence of acute/chronic Hepatitis B or C infection;
6. HIV-1 serostatus (positive or negative, depending on group) confirmed by standard clinical testing;
7. Able to consume soy and nuts safely (in order to consume the standardized meal).

General Exclusion Criteria:

1. History of heavy drinking on a weekly or more frequent basis, with heavy drinking defined per NIAAA guidelines (≥4 drinks for women, ≥5 drinks for men on a given day), in the past two years;
2. More than five heavy drinking episodes in past 90 days;
3. Seeking or receiving treatment for alcohol/drug use, with exception of smoking cessation treatment;
4. Antibiotic use in past 1 month;
5. Daily use of non-steroidal anti-inflammatory drugs, which are known to increase gut permeability;
6. Disorder of the lower GI tract (e.g., inflammatory bowel disease, ulcerative colitis);
7. Positive urine test for amphetamine, cocaine, methamphetamine, opioids, or benzodiazepines (cannabis use will be assessed but is not an exclusion criterion);
8. Positive screening for past 12-month drug use disorder, indicated by Drug Abuse Screening Test-10 score >2;
9. Current major psychiatric disorder (current major depressive episode, bipolar disorder, psychotic disorder);
10. History of fainting, weakness, infection, excessive bruising, or extreme distress from blood draw;
11. Safety contraindication for MRI (e.g., metal implant); Note: copper intrauterine devices (IUDs) continue to be excluded due to Brown MRI research facility regulations but other non-metal IUDs are allowed;
12. Head trauma with loss of consciousness >10 min;
13. Inability to abstain from nicotine for 8 hours in-session;
14. For cannabis users: inability to abstain for 48 hours prior to study;
15. Pregnant, breastfeeding, or not using effective birth control;
16. Any other clinical condition or therapy that, in the physician's opinion, would make subject unsuitable for study or unable to comply with dosing requirement.

HIV-Specific Inclusion Criteria:

1. On antiretroviral therapy (ART) for ≥6 mos;
2. Labs in past 6 mos showing viral load <100 copies/mL, hemoglobin ≥10.0 g/dL, neutrophil count ≥1,000 cells/μL, and platelet count ≥150,000/μL;
3. No active AIDS diagnosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alcohol, ethyl, moderate dose; 0.6 gram ethyl alcohol per kilogram of body weight	Other: Alcohol, ethyl, moderate dose; Moderate oral dose of ethyl alcohol
Placebo Comparator: Placebo; 0 gram ethyl alcohol per kilogram of body weight	Other: Placebo; Placebo beverage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Biomarker of Microbial Translocation	Lipopolysaccharide (LPS), measured in pg/ml	0-3 hours
Plasma Biomarkers of Immune Activation	soluble cluster of differentiation 163 (sCD163), measured in ng/ml	0-3 hours
Cerebral Metabolites	Magnetic resonance spectroscopy will be used quantify cerebral metabolites in brain regions of interest, specifically frontal lobe. Primary metabolites of interest include the summed peak of glutamate and glutamine; choline.	5 hours
White Matter Diffusivity	Diffusion-weighted MRI will be used to quantify diffusivity metrics in brain white matter. Primary outcome is fractional anisotropy (measured on a scale of 0-1, where 1 reflects total anisotropy).	5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Intoxication	Intoxication rating scale (0-10), where a higher rating indicates greater subjective feelings of alcohol intoxication. Participants rate their maximum level of intoxication during the study.	0-5 hours
Cognitive Functioning	Repeatable Battery for Assessment of Neuropsychological Status standardized scores; Note: this measure was unable to be administered to due coronavirus (COVID-19) pandemic restrictions related to social distancing.	0-2 hours

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: The Miriam Hospital; National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Mollie Monnig, PhD, Brown University

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2021
• Primary Completion (Actual): July 2, 2024
• Study Completion (Actual): July 2, 2024

Study Registration Dates

• First Submitted: July 9, 2019
• First Submitted That Met QC Criteria: August 7, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: alcohol; inflammation; brain; HIV infection
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Drinking Behavior; Pathological Conditions, Signs and Symptoms; Behavior; HIV Infections; Alcohol Drinking; Inflammation; Organic Chemicals; Alcohols; Ethanol
• Other Study ID Numbers: 1904002429; P20GM130414 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data generated by this study will be made available to outside investigators in accordance with NIH guidance and policies on data sharing. Data will be available in summary form and as raw individual-level data for analysis.
• IPD Sharing Time Frame: Individual-level data will be available after papers are accepted for publication.
• IPD Sharing Access Criteria: Institutions and individuals wishing to access data must contact the Principal Investigator (Peter Monti, PhD). Persons requesting data must do so in writing, identifying the affiliation and how the data will be used. Co-authorship is not required as a condition for receiving data. Users will agree that the recipient must not transfer the data to other users and that the data are only to be used for research purposes. Requestors will be required to sign a data and biospecimen sharing agreement with further stipulations for data use and security.
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No