Gut Microbiota-Mediated Inflammatory Interactions Between AUD and HIV Infection

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.