A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection

Michael P. Dubé, Ellen S. Chan, Jordan E. Lake, Brett Williams, Jennifer Kinslow, Alan Landay, Robert W. Coombs, Michelle Floris-Moore, Heather J. Ribaudo, Kevin E. Yarasheski

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to glucoregulation. We evaluated inflammation and immune markers in suppressed human immunodeficiency virus (HIV) infection during treatment with the DPP-4 inhibitor sitagliptin. Methods: Virologically suppressed adults with HIV without diabetes on stable antiretroviral therapy (ART) with ≥100/μL CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/day vs placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15-16. Results: Ninety participants were randomized, and 42 from each arm were included in per-protocol analyses. Participants were 45% non-Hispanic white, 38% non-Hispanic black, and 15% Hispanic, with a median age of 51 years; 83% were male; and the median CD4 count was 602 cells/μL. At week 15-16, there was no difference in sCD14 change between the 2 arms (P =. 69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% confidence interval,-57% to-35%) at week 15 (P <. 001). There were no significant between-arm differences in other soluble biomarkers, total CD4 and CD8 counts, or markers of lymphocyte or monocyte activation. Sitagliptin was well tolerated. Conclusions: Sixteen weeks of sitagliptin had no effect on sCD14 levels in virologically suppressed participants with HIV. CXCL10, a chemokine involved in atherogenesis that predicts non-AIDS events during ART, declined markedly with sitagliptin. This suggests that DPP-4 inhibition has the potential to reduce cardiovascular morbidity in treated HIV infection. Clinical Trials Registration: NCT01426438.

Original languageEnglish (US)
Pages (from-to)1165-1172
Number of pages8
JournalClinical Infectious Diseases
Volume69
Issue number7
DOIs
StatePublished - Sep 13 2019
Externally publishedYes

Keywords

  • CXCL10
  • dipeptidyl peptidase-4 inhibitor
  • HIV
  • inflammation
  • soluble CD14

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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