A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection
A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection
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DOI：
10.1093/cid/ciy1051
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发表时间：
2019-10-01
影响因子：
11.8
通讯作者：
Yarasheski, Kevin E.
中科院分区：
文献类型：
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作者：
Dube, Michael P.;Chan, Ellen S.;Yarasheski, Kevin E.
背景。二肽基肽酶-4 （DPP-4）抑制剂除了调节血糖外，还具有多种抗炎和免疫调节作用。我们评估了DPP-4抑制剂西格列汀治疗期间抑制人类免疫缺陷病毒（HIV）感染的炎症和免疫标志物。在一项多中心试验中，病毒学抑制的成人HIV无糖尿病患者接受稳定抗逆转录病毒治疗（ART）， CD4细胞浓度为>= 100/ μ L，随机分为西格列汀100 mg/天和安慰剂组，为期16周。主要终点是血浆可溶性CD14 （sCD14）从基线到第15-16周的变化。90名参与者被随机化，每组42人被纳入方案分析。参与者是非西班牙裔白人45%，非西班牙裔黑人38%，西班牙裔15%，中位年龄51岁；83%为男性；中位CD4计数为602个细胞/ μ l。在第15-16周，两组间sCD14变化无差异（P = 0.69）。相对于安慰剂，西格列汀组在第15周时CXCL10下降了47%(95%置信区间，-57%至-35%)（P < 0.001）。其他可溶性生物标志物、总CD4和CD8计数、淋巴细胞或单核细胞活化标志物在两组间无显著差异。西格列汀耐受性良好。16周的西格列汀治疗对病毒学抑制的HIV患者的sCD14水平没有影响。CXCL10是一种参与动脉粥样硬化的趋化因子，在抗逆转录病毒治疗期间预测非艾滋病事件，西格列汀显著降低。这表明抑制DPP-4有可能降低接受治疗的HIV感染患者的心血管发病率。
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/mu L 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/mu L. 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.