DPP-4 inhibition Potentially Reduces Atherogenesis in Some PLWHIV

Treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, had no effect on soluble CD14 when given to participants with virally suppressed HIV infection, according to findings published in Clinical Infectious Diseases.

DPP4 inhibitors appear to have many effects aside from the glucoregulatory actions, and may benefit cardiometabolic function, as well as contribute to anti-inflammatory, immune regulatory, and hematopoietic effects. Results from small pilot studies suggested that participants with controlled HIV infection who did not have type 2 diabetes did not experience an adverse effect with sitagliptin, with regard to plasma HIV RNA or CD4 T-cell counts.

 In addition, improvement was observed in select soluble inflammatory biomarkers. In the current multicenter trial, inflammation and immune markers were evaluated in 90 individuals with suppressed HIV infection and without type 2 diabetes, who were treated with sitagliptin. All participants had a CD4 count ≥100/mm³ and were randomly assigned to either 16 weeks of sitagliptin 100 mg/day (n=45) or placebo (n=45). The primary endpoint was any change in plasma-soluble CD14, because it has a strong correlation with mortality and morbidity in individuals receiving antiretroviral therapy, as well as with several well-known HIV comorbidities.

At the end of the study period (week 15/16), no differences in soluble CD14 levels were observed between the 2 groups. Of note, however, participants in the sitagliptin group had a median 50.5% decline from baseline in CXCL10 at week 15 compared with the placebo group. In addition, the participants in the sitagliptin group have a median increase of 70.6% in CXCL10 levels during the posttreatment period. CXCL10 is a chemokine that has been implicated in cardiovascular disease and atherogenesis and distal sensorimotor polyneuropathy, and predicts non-AIDS events in people receiving antiretroviral therapy. No significant events were observed between groups for soluble CD163, soluble CD26, interleukin 6, C-reactive protein, soluble tumor necrosis factor receptors I and II, and total CD4 and CD8 counts, as well as markers of lymphocyte or monocyte activation.

“More work is needed to determine the implications of these findings,” concluded the researchers.

Reference

Dubé MP, Chan ES, Lake JE, et al. A randomized, double-blinded, placebo-controlled trial of sitagliptin for reducing inflammation and immune activation in treated and suppressed HIV infection [published online December 10, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy1051

This article originally appeared on Infectious Disease Advisor