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.

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.

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.

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.

Individual-level data will be available after papers are accepted for publication.

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.

For the duration of a participants' participation (an average of three months from baseline to completion).