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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
DOUBLE
Enrollment
38
Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48.
John A. Burns School of Medicine, University of Hawaii - Manoa
Honolulu, Hawaii, United States
RECRUITINGCD4 T cell PD1+TIGIT+
Comparison of change over time in percentage of CD4 T cells bearing the PD1+TIGIT+ surface markers in peripheral blood mononuclear cells (PBMC) in the treatment (metformin) arm compared to the observation arm
Time frame: Entry to week 72
CD8 T cell PD1+TIGIT+
Comparison of change over time in percentage of CD8 T cells bearing the PD1+TIGIT+ surface markers in PBMCs in the 2 study arms
Time frame: Entry to week 72
Plasma levels of indoleamine 2,3-dioxygenase (IDO)
Comparison of change over time in the levels of IDO \[assessed as a ratio of L-kynurenine (kyn) to substrate tryptophan (trp)\] in mass spectrometry assays
Time frame: Entry to week 72
Peripheral blood CD4 T cell intracellular HIV DNA
Comparison of change over time in the number of intracellular HIV DNA copies per million CD4 T cells in PBMC in the 2 study arms
Time frame: Entry to week 72
Peripheral blood CD4 T cell intracellular HIV RNA
Comparison of change over time in the number of intracellular HIV RNA copies per million CD4 T cells in PBMC in the 2 study arms
Time frame: Entry to week 72
Peripheral blood monocyte intracellular HIV DNA
Comparison of change over time in the number of intracellular HIV DNA copies per million monocytes in PBMC in the 2 study arms
Time frame: Entry to week 72
Peripheral blood monocyte intracellular HIV RNA
Comparison of change over time in the number of intracellular HIV RNA copies per million monocytes in PBMC in the 2 study arms
Time frame: Entry to week 72
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