Impact of Metformin on Immuno-virologic Parameters in HIV

A 72 Week, Randomized, Open-label vs Observation Study to Assess the Potential Immuno-virologic Benefit of Metformin in HIV-infected Individuals Receiving Antiretroviral Therapy

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.

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