Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use

Exclusion Criteria

• •Inability to give informed consent.
• •Refusal or inability to have blood drawn.
• •Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, platelet disorder requiring precautions).
• •Pregnant or nursing individuals.
• •Diabetes mellitus.
• •History of severe renal impairment or eGFR \<60 mL/min/1.73m².
• •Creatinine clearance \<60 mL/min.
• •History of liver disease.
• •ALT/AST \> 3× the upper limit of normal.
• •Total bilirubin \>1.4 mg/dL.
• •Albumin \<3.5 g/dL.
• •Prothrombin \>1.5× the upper limit of normal.
• •AUDIT-C score ≥8.
• •Hemoglobin \<9.0 g/L.
• •Absolute neutrophil count \<1,000/mL.
• •Platelet count \<100,000/mL.
• •History of acute or chronic metabolic acidosis.
• •Serum bicarbonate \<22 mEq/L.
• •Anion gap \>10 mEq/L.
• •Serum lactate \>2.2 mmol/L.
• •Serum vitamin B12 \<250 pg/mL.
• •History of chronic diarrhea.
• •Current use of metformin or other diabetes medications.
• •History of myocardial infarction, endocarditis, stroke, heart failure, chronic obstructive pulmonary disease, or sepsis.
• •Use of medications such as furosemide, nifedipine, ranolazine, vandetanib, or cimetidine (current or within the past 30 days).
• •Active hepatitis B infection.
• •Hepatitis C infection within 6 months of study entry; individuals with prior hepatitis C must be at least 6 months post-treatment with direct-acting antivirals.
• •Previous receipt of Jynneos or pneumococcal vaccine within the past two years (self-report).
• •Severe allergic reaction to metformin, Jynneos, or Capvaxvie (self-report). Blood donations exceeding 450 mL in the 8 weeks prior to enrollment, accounting for study-related blood draws.
• •Any medical, psychiatric, social condition, or responsibility that, in the investigator's judgment, could interfere with study procedures.