Metformin for HIV Inflammation

Open-Label, Randomized, 24-Week Pilot Study of Metformin vs Observation for Persistent Immune Activation in Chronic HIV Infection

This proposal seeks to assess the impact of 24 weeks of metformin on non-calcified plaques and calcified plaques assessed by coronary CT angiography, and on whether these changes can be explained by metformin-induced phenotypic and secretory changes of monocytes.

Inclusion Criteria:

• HIV+
• on suppressive ART stable for > 1 year
• Age > 45 years
• Ability and willingness to provide written informed consent

Exclusion Criteria:

• Uncontrolled chronic medical condition or cancer
• Acute illness within 2 weeks of entry
• Diagnosis of diabetes or impaired fasting glucose
• Chronic diarrhea
• Known hypersensitivity or contraindication to metformin use
• Hepatitis C co-infection
• Serum B12 level below the reference normal range as listed by the commercial laboratory (Diagnostic Laboratory Services)
• Pregnancy, or intent to become pregnant
• Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.
• Current or past history of coronary artery disease or congestive heart failure
• Resting heart rate > 100 beats/min
• Presence of conduction abnormalities or pathologic arrhythmia on EKG
• The following lab values: Hemoglobin < 9.0 g/dL; Absolute neutrophil count < 1000/μL; Platelet count < 50,000/μL; and AST (SGOT) and ALT (SGPT) > 5x ULN
• Calculated creatinine clearance (Cockcroft and Gault) < 60 ml/min
• Patients over 450 lbs
• History of iodine allergy or X-ray contrast allergy
• History of allergy to metoprolol
• Active or recent past history (within past 2 years) of illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with the protocol requirements
• Patients in whom there are other reasons that the CAC/CTA procedure is contra-indicated or who are at higher risk of adverse events
• Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable