Immunological alterations with GLP‐1 agonists in people living with HIV

Abstract

Dear Editor, Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have become an important therapeutic option in the management of type 2 diabetes (T2D) and obesity. According to a recent viewpoint published in this journal, clinical experience in people living with HIV is limited to two clinical cases [1]. While calling for further investigations, the authors concluded no theoretical efficacy or safety concerns for GLP-1 RAs in this scenario.As indirect incretin mimetics such as dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to decrease circulating CD4 T-cells [2], we hypothesized whether direct incretin mimetics such as GLP-1 RAs might also be associated with immunological alterations. Taking advantage of the availability of immunological data obtained in people living with HIV during routine care, we performed a retrospective study on potential changes in circulating CD4 and CD8 T-cell counts during GLP-1 RA treatment. All CD4 and CD8 T-cells from the period 1 year before and after initiation of GLP-1 RA treatment were collected in people living with HIV with T2D and/or obesity who had been treated with dulaglutide or semaglutide once-weekly in two large outpatient HIV centres. Analysis was restricted to subjects with at least one determination during GLP-1 RA treatment, with stable viral suppression (<50 HIV RNA copies/mL), and without evidence of malignant disease or exposure to immunosuppressive drugs during the observation period. A sample size of 67 was calculated based on a one-sided paired t-test, assuming the difference between the two groups to be 100 cells/μL or more, using the pooled standard deviation from published data for the use of DPP-4 inhibitors [2]. Statistical analyses were performed using R 4.3.1.Overall, data from 70 people living with HIV (37 were treated with semaglutide, 33 with dulaglutide) were analyzed, comprising 534 measurements of CD4 and CD8 T-cell counts. Most subjects were male (84.3%), of Caucasian ethnicity (90.0%), and in the age group of 40-59 years (75.7%); T2D was present in 55.7%, and median body mass index at baseline was 33 kg/m 2 (interquartile range [IQR] 28-37 kg/m 2 ). Median absolute and relative CD4 T-cell nadir counts were 303 cells/μL (IQR 189-421) and 20% (IQR 14-26), respectively.