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

TL;DR

This study found no significant immune benefits from metformin in people with HIV and type 2 diabetes over two years.

Contribution

The study provides new evidence on metformin's lack of immune reconstitution effects in a matched HIV and T2DM cohort.

Findings

No significant difference in CD4 T-cell count change between metformin-treated and control groups.

No significant difference in CD4/CD8 ratio change between the two groups.

Subgroup analyses showed no immune benefits in individuals with low baseline CD4 counts.

Abstract

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.

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).

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.

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

We observed no significant differences in immune reconstitution (measured by CD4 T cell count and CD4/CD8 ratio) between metformin treated individuals and matched controls over a 2-year follow-up period.

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