Summary
Non-diabetic, aviremic HIV-infected individuals on antiretroviral therapy (ART) will be randomized to metformin therapy or to observation for 72 weeks. Primary objective is to assess change over 72 weeks in CD4 T cell negative checkpoint receptors (PD-1 and TIGIT). As secondary objectives the study will look at 72 week change in other immuno-virologic parameters (CD8 T cell negative checkpoint receptors, plasma indoleamine 2,3-dioxygenase (IDO) levels and CD4 T cell and monocyte intracellular HIV DNA and HIV RNA. The study will also explore the 72 week impact of metformin on change in carotid intima-media thickness (cIMT) as a surrogate marker of atherosclerosis, on neuropsychological (NP) performance, strength, and change in body composition.
Eligibility Criteria
Age Range: 40 years to No maximum
Inclusion Criteria:
* HIV+
* On suppressive ART stable for \> 1 year
* Plasma HIV RNA \< 50 copies/mL within 3 months of entry, with no HIV RNA \> 200 copies/mL within the past 6 months prior to entry
* Age \>40 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 by history, fasting blood glucose \>126, or by HgbA1c \> 6.5
* Chronic, uncontrolled diarrhea
* Known hypersensitivity or contraindication to metformin use
* Current presence of hepatitis C including currently on or intent to start therapy for hepatitis C within the 48 week duration of study.
* Serum B12 level below the reference normal range as listed by the commercial lab utilized for this study (Diagnostic Laboratory Services)
* Pregnancy, or intent to become pregnant or nursing an infant
* Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.
* Current uncontrolled coronary artery disease or NYHA Class 3 or 4 congestive heart failure
* History of liver cirrhosis
* Current use of zidovudine, stavudine or didanosine
* The following lab values
* Hemoglobin \< 9.0 g/dL
* Absolute neutrophil count \< 1000/μL
* Platelet count \< 50,000/μL
* AST (SGOT) and ALT (SGPT) \> 5x upper limit of normal (ULN)
* Calculated creatinine clearance (Cockcroft and Gault) \< 50 ml/min
* 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, 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