A Randomized, Double-Blinded, Placebo-Controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed HIV Infection.

TitleA Randomized, Double-Blinded, Placebo-Controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed HIV Infection.
Publication TypeJournal Article
Year of Publication2018
AuthorsDubé MP, Chan ES, Lake JE, Williams B, Kinslow J, Landay A, Coombs RW, Floris-Moore M, Ribaudo HJ, Yarasheski KE
Corporate AuthorsACTG 5346 Team
JournalClin Infect Dis
Date Published2018 Dec 10
ISSN1537-6591
Abstract

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to their glucoregulatory actions. We evaluated inflammation and immune markers in suppressed HIV infection during treatment with the DPP-4 inhibitor sitagliptin.

Methods: Virologically suppressed adults with HIV without diabetes mellitus on stable ART with ≥100/mm 3 CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/d vs. placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15/16. Additional soluble biomarkers, and lymphocyte and monocyte activation were assessed.

Results: Ninety participants were randomized, and 42 from each arm were included in per-protocol analyses. Evaluable participants were 45% non-Hispanic white, 38% non-Hispanic black, 15% Hispanic, median age of 51 years, 83% male, with median CD4 count 602 cells/mm 3. At week 15/16, there was no difference in sCD14 change between the two arms (p=0.69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% CI:-57,-35) at week 15 (p<0.001). There were no significant between-arm differences in soluble CD163, soluble CD26, interleukin-6, C-reactive protein, soluble tumour necrosis factor receptors I and II, 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.

DOI10.1093/cid/ciy1051
Alternate JournalClin. Infect. Dis.
PubMed ID30535188