Metformin Treatment and Immune Reconstitution in People With HIV and Type 2 Diabetes: A Matched Retrospective Study

Abstract

Background: Despite effective antiretroviral treatment (ART), HIV infection is associated with immune dysfunction and inflammation. Metformin has shown beneficial immunological and anti-inflammatory effects, including in people with HIV (PWH). We studied the potential association between metformin treatment and immune reconstitution in PWH.

Methods: We conducted a retrospective cohort study set in Stockholm, Sweden. PWH with T2DM who initiated metformin treatment after at least 2 years on effective ART (exposed individuals) and metformin-naïve PWH (controls) were matched in a 1:1 ratio based on age, sex, baseline immune status, and duration of ART. Outcomes included mean values of CD4 cell counts and CD4/CD8 ratios from 1.5 years to 3.5 years after compared with 2 years before the exposed individual started metformin treatment (index date).

Results: Among 1332 PWH, 43 metformin-exposed individuals (median age, 48 years; 11 years since start of ART) with T2DM and 43 nondiabetic controls (median age, 47 years; 11 years since start of ART) were included in the matched analyses. The median (interquartile range) change in CD4 T-cell count was 35 (-21 to 125) cells/μL among exposed individuals and 48 (-18 to 100) cells/μL among controls (P = .96). The corresponding numbers were 0.10 (0.03 to 0.20) and 0.08 (0.02-0.16) for CD4/CD8 ratio (P = .18). No differences were observed in subgroup analyses of PWH with low CD4 T-cell counts and CD4/CD8 ratios.

Conclusions: No significant differences in immune reconstitution were observed between metformin-treated individuals and matched controls over the 2-year follow-up period.

Keywords: CD4; CD4/CD8; HIV; diabetes; metformin.

Figure 1.

Study flowchart. Abbreviations: ART, antiretroviral treatment; PWH, people with HIV; T2DM, type 2 diabetes mellitus.

Figure 2.

Outcome (A and B) and change (C and D) in CD4 T-cell counts and CD4/CD8 ratios in exposed individuals (n = 43) and matched controls (n = 43). The boxes represent medians with 25th and 75th percentiles. P values were obtained from the Wilcoxon signed-rank test. The changes in CD4 T-cell counts and CD4/CD8 ratios were obtained by calculating the average values from the outcome period (1.5–3.5 years after the index date) minus the baseline period (2 years to 1 day before the index date).

Figure 3.

Outcome (A and B) and change (C and D) in CD4 T-cell counts and CD4/CD8 ratios in exposed individuals and matched controls with low baseline values (CD4 <500 cells/μL: 11 exposed individuals, 11 controls; CD4/CD8 <1: 30 exposed individuals, 30 controls). The boxes represent medians with 25th and 75th percentiles. P values were obtained from the Wilcoxon signed-rank test. The changes in CD4 T-cell counts and CD4/CD8 ratios were obtained by calculating the average values from the outcome period (1.5–3.5 years after the index date) minus the baseline period (2 years to 1 day before the index date).

Figure 4.

A and B, Outcome and change (C and D) in CD4 T-cell counts and CD4/CD8 ratios in exposed individuals with an effective daily dose of metformin <1000 mg (low dose, n = 12) vs ≥1000 mg (high dose, n = 31). The boxes represent medians with 25th and 75th percentiles. A dose of <1000 mg daily was characterized as low and ≥1000 mg as high. P values were obtained from the Wilcoxon signed-rank test. The changes in CD4 T-cell counts and CD4/CD8 ratios were obtained by calculating the average values from the outcome period (1.5–3.5 years after the index date) minus the baseline period (2 years to 1 day before the index date).