Gut Microbiota-Mediated Inflammatory Interactions Between AUD and HIV Infection

June 2, 2026 updated by: Ali Keshavarzian, Rush University Medical Center

Gut Microbiota-Mediated Inflammatory Interactions Between Alcohol Use Disorders and HIV Infection

Alcohol use disorder (AUD) has been associated with high prevalence of inflammation-associated co-morbidities in people living with HIV even those receiving effective antiretroviral therapy (ART). Our preliminary data support a model in which the combined insult of AUD and HIV on the gut, specifically on the microbiota and intestinal barrier integrity, exacerbates inflammation. Our preliminary data using intestinal organoids also suggest a potential mechanism for AUD-mediated changes in the gut barrier function during HIV; the intestines of HIV+ individuals have low resilience to alcohol induced intestinal barrier disruption caused by high levels of oxidative stress. Finally, our preliminary data also suggest a potential approach to enhance the integrity of the intestinal barrier and reduce gut derived inflammation in people living with HIV with/without AUD- short chain fatty acid prebiotics. These prebiotics prevent alcohol mediated adverse effects on the intestinal barrier and inflammation by preventing oxidative stress. These prebiotics are safe and decrease gut inflammation in humans.

40 HIV+ ART+ (20 AUD- and 20 AUD +), will be recruited for a prebiotic intervention. This is a proof-of-concept intervention study to establish a causal link between microbiota-gut and HIV pathology during ART by asking whether modifying microbiota and gut milieu impacts intestinal barrier function, systemic inflammation, and brain pathology in HIV+ people. Participants will complete three in-person clinic visits and four virtual check-in visits during this 8 week study. This study uses a crossover design. At baseline, participants will be randomized to receive either a prebiotic or a placebo for the first intervention period. After completing this period, participants will cross over to receive the alternate study product for the second intervention period, allowing each participant to serve as their own control. These participants are part of the larger observation study (n=160), which will test the hypothesis that intestines from HIV+ individuals have lower resilience to alcohol mediated gut barrier disruption than intestines from HIV-negative controls. New participants will also be recruited. Blood, urine, and stool, will be collected from participants to compare intestinal barrier integrity, system and gut inflammation, immune activation, oxidative stress, microbiome/metabolome. and HIV reservois.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age 21 to 75 years men and women
  • Infection with HIV-1, as documented by a licensed ELISA and confirmed by a Western blot or HIV-1 RNA
  • On ART for at least 12 months. No history of zidovudine (AZT) or stavudine (D4T) use.
  • No change in ART for at least 6 months.
  • CD4+ T cell count of > 250 cells/µl, nadir CD4+ T cell count of > 250 cells/µl
  • Plasma HIV-1 RNA level consistently below the limit of detection of commercial ultrasensitive assay (usually <20 copies/mL) for at least six months before study entry.
  • For those for "AUD group" AUDIT-C =/> 4 for men and = ≥3 for women.
  • Documented BMI between 25-40
  • Ability and willingness to provide informed consent

Exclusion criteria:

  • Receipt of a non-HIV vaccine within 30 days
  • Opportunistic infection within 30 days
  • Immunosuppressive medications (e.g., systemic corticosteroids, tacrolimus, sirolimus, mycophenolate, azathioprine, interferon, and cancer chemotherapy) within 90 days
  • History of clinically significant medical disease that could potentially impact the integrity of intestinal barrier function or microbiota including renal (creatinine >2 mg/dL), liver (documented cirrhosis based on histology or ALT/AST greater than 2 1/2 times normal), cardiac failure (NY classification III/IV), or uncontrolled diabetes (Hgb-A1c>8%).
  • Fiber intake > 15 grams.
  • Chronic HBV and un-treated HCV (documentation of cure can be enrolled)
  • Herbal/botanical supplements with potential microbiome or anti-inflammatory effects (e.g., inulin/chicory fiber, berberine, high-dose polyphenols). Participants will be eligible to participant if they discontinue use for at least 2 weeks before enrollment.
  • Regular use of medications that affect intestinal permeability including NSAIDs (daily more than three days a week during the prior two weeks). Type and frequency and duration of NSAID (those taking less than 3 /per week) should be recorded. If participants need to take antibiotics or NSAIDS during the study, duration, name, and dosage will be recorded but they will not be excluded.
  • Antibiotics (during or prior) four weeks to enrollment. Type and duration of antibiotic treatment within 90 days should be recorded.
  • Current use of a restrictive or specialty diet like vegan, vegetarian, gluten-free, Paleo, or any specific carbohydrate diet because these diets can impact the microbiota community.
  • Use of herbal, botanical, or nutraceutical supplements with potential effects on the gut microbiome or systemic inflammation. This includes:

prebiotic fibers such as inulin, chicory root, fructooligosaccharides (FOS), or galactooligosaccharides (GOS) botanical or herbal compounds with microbiome-modulating or anti-inflammatory properties, such as berberine, curcumin, resveratrol, or high-dose polyphenol Probiotics or synbiotics Digestive enzymes or other nutraceuticals reported to alter gut microbial composition.

Potential participants may enroll if they discontinue use for at least 2 weeks before enrollment. Type, dosage, frequency, route of administration (for example oral), and date last taken will be documented at time of enrollment verify that a sufficient washout period has occurred before enrollment.

-Have undergone bowel preparation or colonic (e.g., for a colonoscopy or similar procedure) for example, within 4 weeks prior to enrollment.

Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease). Celiac disease. GI cancers

  • Gastrointestinal surgeries/resection (cholecystectomy is accepted but should be recorded)
  • Currently taking or planning to start a GLP-1 receptor agonist or dual GLP-1/GIP receptor agonist for weight loss or weight management. This includes medications such as semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), exenatide (Byetta, Bydureon), lixisenatide (Adlyxin), and tirzepatide (Mounjaro, Zepbound). Participants who previously used these medications may be eligible if they discontinued use at least 4 weeks prior to enrollment. For eligible individuals, the medication name, dosage, frequency, route of administration (for example injection or oral), and date of last dose will be documented at enrollment. The study team will document the last dose to verify that a sufficient wash out period has occurred before enrollment and to account for any possible microbiome differences.
  • Use of PPI is accepted but type, dose and duration should be recorded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HIV-infected ART-suppressed individuals with AUD
Only 20 HIV+ ART+,AUD + individuals will be invited to take part in a prebiotic sub study, which they will take a prebiotic for 4 weeks and placebo for 4 weeks.
Dietary supplement: 4 week prebiotic consumption
For this crossover design, participants will be randomly assigned to take a prebiotic or placebo for 4 weeks and then switch to the other products. Participants and research coordinators will be blinded. Participants will be instructed to consume the prebiotic daily during the first three days and then twice daily for the remaining weeks. Participants will be instructed to consume the powder in the morning on the first three days, then in the morning and afternoon for the following weeks. They will record their prebiotic consumption and gastrointestinal symptoms in a daily log and have weekly check-ins with the research coordinator.
Other: 4 week placebo consumption
For this crossover design, participants will be randomly assigned to take a prebiotic or placebo for 4 weeks and then switch to the other products. Participants and research coordinators will be blinded. Participants will be instructed to consume the placebo (maltodextrin) daily during the first three days and then twice daily for the remaining weeks. Participants will be instructed to consume the powder in the morning on the first three days, then in the morning and afternoon for the following weeks. They will record their prebiotic consumption and gastrointestinal symptoms in a daily log and have weekly check-ins with the research coordinator.
Experimental: HIV-infected ART-suppressed individuals with no AUD
Only 20 HIV+ ART+,AUD - individuals will be invited to take part in a prebiotic sub study, which they will take a prebiotic for 4 weeks and placebo for 4 weeks.
Dietary supplement: 4 week prebiotic consumption
For this crossover design, participants will be randomly assigned to take a prebiotic or placebo for 4 weeks and then switch to the other products. Participants and research coordinators will be blinded. Participants will be instructed to consume the prebiotic daily during the first three days and then twice daily for the remaining weeks. Participants will be instructed to consume the powder in the morning on the first three days, then in the morning and afternoon for the following weeks. They will record their prebiotic consumption and gastrointestinal symptoms in a daily log and have weekly check-ins with the research coordinator.
Other: 4 week placebo consumption
For this crossover design, participants will be randomly assigned to take a prebiotic or placebo for 4 weeks and then switch to the other products. Participants and research coordinators will be blinded. Participants will be instructed to consume the placebo (maltodextrin) daily during the first three days and then twice daily for the remaining weeks. Participants will be instructed to consume the powder in the morning on the first three days, then in the morning and afternoon for the following weeks. They will record their prebiotic consumption and gastrointestinal symptoms in a daily log and have weekly check-ins with the research coordinator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sugar test for intestinal permeability after prebiotic and placebo consumption in substudy
Time Frame: 8 weeks
Measure the permeation of sugar probes following an oral test dose of sugars as this is standard for evaluating intestinal barrier integrity
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in stool and intestinal microbiota composition after prebiotic and placebo consumption
Time Frame: 8 weeks
A combination of 16S rRNA gene amplicon sequencing and shotgun metagenome sequencing will be used to characterize microbial community structure in intestinal biopsies and stool.
8 weeks
Change in plasma and stool SCFA level before and after prebiotic treatment
Time Frame: 8 weeks
Mass spectrometry and NMR
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rush University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 5, 2024

Primary Completion (Estimated)

August 31, 2028

Study Completion (Estimated)

August 31, 2029

Study Registration Dates

First Submitted

November 14, 2023

First Submitted That Met QC Criteria

November 14, 2023

First Posted (Actual)

November 18, 2023

Study Record Updates

Last Update Posted (Actual)

June 4, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22112903

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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