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. 2025 Oct;26(10):1585-1599.
doi: 10.1111/hiv.70089. Epub 2025 Aug 1.

Leukocyte count and new-onset diabetes mellitus in people with HIV: A longitudinal study

Sophia C Meyer  1 , Zoe Klein  1 , Isabella C Schoepf  1   2   3 , Christian W Thorball  4 , Marco Labarile  5   6 , Neeltje A Kootstra  7 , Peter Reiss  8 , Lene Ryom  9   10   11 , Dominique L Braun  5   6 , Maria C Thurnheer  2 , Catia Marzolini  12 , Christian R Kahlert  13 , Enos Bernasconi  14 , Matthias Cavassini  15 , Annalisa Marinosci  16 , Jacques Fellay  4   17 , Huldrych F Günthard  5   6 , Roger D Kouyos  5   6 , Bruno Ledergerber  5 , Philip E Tarr  1 ; Swiss HIV Cohort Study
Collaborators, Affiliations

Leukocyte count and new-onset diabetes mellitus in people with HIV: A longitudinal study

Sophia C Meyer et al. HIV Med. 2025 Oct.

Abstract

Objectives: The risk of diabetes mellitus (DM) is increased in people with HIV. Chronic inflammation contributes to DM risk. High leukocytes are associated with DM in the general population, but in people with HIV, evidence of a leukocyte-DM association is limited.

Methods: We included participants of the Swiss HIV Cohort Study with new-onset DM (2000-2023) and matched controls. We obtained uni- and multivariable odds ratios (ORs) for DM, based on traditional and HIV-related DM risk factors, leukocyte count and potential confounders for leukocyte count.

Results: Among 732 DM cases (median age 54 years, 79% male at birth, 86% with suppressed HIV RNA) and 2032 DM-free controls, the latest leukocyte count prior to DM diagnosis was higher in cases than in controls (median [interquartile range], 6200 [5115-7800] vs. 5900/μL [4800-7180]; p < 0.001), but leucocytosis (>11 000/μL) was uncommon (3.8% vs. 2.3%; p = 0.032). DM-OR in the highest vs. lowest leukocyte quintile was 1.91 (95% confidence interval, 1.45-2.52) in univariable analysis and 2.47 (1.71-3.57) in multivariable analysis. For comparison, multivariable DM-OR for dyslipidaemia, overweight, ≥12-month stavudine exposure and ≥12-month integrase inhibitor exposure were 2.23 (1.80-2.75), 2.83 (2.21-3.62), 1.54 (1.16-2.04) and 2.29 (1.13-4.62), respectively. We found no relevant confounders for the leukocyte-DM association. Leukocytes were significantly associated with DM up to 10 years before diagnosis (all p < 0.02).

Conclusions: High leukocyte count is an independent DM risk factor in people with HIV in Switzerland and increases the risk of DM to a degree similar to traditional and HIV-related risk factors, up to 10 years before DM diagnosis.

Keywords: HIV infection; diabetes mellitus; leukocytes; multivariable analysis; white blood cells.

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Conflict of interest statement

PR reports unrestricted scientific grant support from Gilead Sciences, ViiV Healthcare and Merck; consulting fees from Gilead Sciences and ViiV Healthcare; and fees from ViiV Healthcare for chairing and providing an introduction to a workshop; all paid to his institution and unrelated to the submitted work. DLB reports consulting fees from Gilead, MSD and ViiV; personal fees for educational work as well as support for attending meetings from Gilead, MSD and ViiV; and personal fees for participation on a Data Safety Monitoring or Advisory Board from Gilead, MSD, ViiV, AstraZeneca, and Pfizer, outside the submitted work. CM has received personal fees for educational work from Gilead Sciences and ViiV Healthcare outside the submitted work. EB has received grants from the Swiss National Science Foundation and Merck; consulting fees from AstraZeneca; fees for educational work from Pfizer AG Switzerland; support for attending meetings and/or travel from Gilead Sciences, Merck, ViiV Healthcare and Pfizer AG Switzerland; and fees for participation on the Data Safety Monitoring or Advisory Board from Gilead Sciences, ViiV Healthcare, Merck, Pfizer AG Switzerland, AbbVie, AstraZeneca, Moderna and Eli Lilly, all paid to his institution and outside the submitted work. MC reports research grants from Gilead, MSD and ViiV; fees for expert testimony from Gilead, MSD and ViiV; and support for attending meetings from Gilead, all paid to his institution outside the submitted work. HFG has received grants from the Swiss National Science Foundation, Swiss HIV Cohort Study, Yvonne Jacob Foundation, University of Zurich's Clinical Research Priority Program, Zurich Primary HIV Infection, Systems.X, Bill and Melinda Gates Foundation, NIH, Gilead Sciences, ViiV and Roche; personal fees from Merck, Gilead Sciences, ViiV, Janssen, GSK, Johnson & Johnson and Novartis for consultancy or data and safety monitoring board membership; and a travel grant from Gilead. BL received personal fees from Kantonsspital Baselland, Liestal, Switzerland, during the conduct of the study and reports personal fees from Gilead, outside the submitted work. PET's institution reports unrestricted and educational grants from Gilead, ViiV and MSD and advisory fees from Gilead and ViiV, all outside the submitted work. All other authors report no potential conflicts.

Figures

FIGURE 1
FIGURE 1
Study flowchart. SHCS, Swiss HIV Cohort Study.
FIGURE 2
FIGURE 2
(a, b) Descriptive longitudinal trends for leukocyte count and HIV RNA in cases and controls. Descriptive (observed) trajectories over time for controls versus cases. Panel A shows leukocytes, and panel B shows HIV RNA. Depicted are counts (line) and 95% confidence intervals (shaded areas), which were created with local polynomial smoothing. Only parameters from regular (per protocol) 6‐monthly follow‐up SHCS visits up until the matching date were considered. Data of all participants irrespective of observation duration are shown in the graphs (open cohort design). Graphs for participants with ≥15 years observation time (closed cohort design) are shown in Figure S2A,B.
FIGURE 3
FIGURE 3
Odds ratios (ORs) for diabetes mellitus (DM; with 95% confidence intervals [CIs]), according to clinical risk factors and latest leukocyte quintiles. Univariable and bivariable conditional logistic regression of associations of latest leukocyte count with new‐onset DM for 732 cases and 2032 controls are shown. DM‐OR was significantly higher in the fifth (highest) than in the first (lowest) leukocyte quintile in univariable and in multivariable analysis, adjusted for all variables shown. Table 1 shows all odds ratios and 95% confidence intervals. Median leukocyte counts (cells/μL) in cases and controls in the different categories are shown on the right‐hand side. ART, antiretroviral therapy; BMI, body mass index; CI, confidence interval; EFV, efavirenz; HCV, hepatitis C virus; IDU, intravenous drug use; INSTI, integrase inhibitor; MSM, men who have sex with men; NNRTI, non‐nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
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