1. A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection.
- Author
-
Dubé MP, Chan ES, Lake JE, Williams B, Kinslow J, Landay A, Coombs RW, Floris-Moore M, Ribaudo HJ, and Yarasheski KE
- Subjects
- Adult, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents adverse effects, Antiretroviral Therapy, Highly Active, Biomarkers, CD4 Lymphocyte Count, Female, HIV immunology, HIV Infections immunology, HIV Infections metabolism, Humans, Immunologic Factors administration & dosage, Immunologic Factors adverse effects, Male, Middle Aged, Sitagliptin Phosphate administration & dosage, Sitagliptin Phosphate adverse effects, Treatment Outcome, Viral Load, Anti-Inflammatory Agents therapeutic use, HIV drug effects, HIV Infections drug therapy, HIV Infections virology, Immunologic Factors therapeutic use, Sitagliptin Phosphate therapeutic use
- 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., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
- Full Text
- View/download PDF