1.
Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s.
Kelesidis, T, Tran, TT, Stein, JH, Brown, TT, Moser, C, Ribaudo, HJ, Dube, MP, Murphy, R, Yang, OO, Currier, JS, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2015;(4):651-60
-
-
Free full text
-
Abstract
BACKGROUND It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs). METHODS In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control. RESULTS Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups. CONCLUSIONS Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens. CLINICAL TRIALS REGISTRATION NCT00811954 and NCT00851799.
2.
Effects of postoperative immune-enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome.
Jiang, XH, Li, N, Zhu, WM, Wu, GH, Quan, ZW, Li, JS
Chinese medical journal. 2004;(6):835-9
Abstract
OBJECTIVE This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome of patients undergoing major abdominal surgery. METHODS This study was designed as a multicenter, prospective, randomized and controlled clinical trial. One hundred twenty-four patients undergoing major abdominal surgery were randomly assigned to receive either an immune enhancing enteral diet or an isocaloric and isonitrogenous control enteral diet for seven days. Enteral feeding was initiated 24 hours after surgery. Host immunity was evaluated by measuring levels of IgG, IgM, IgA, CD4, CD8, and CD4/CD8, and the inflammatory response was determined by assessing IL-1alpha, IL-2, IL-6, IL-10, and TNF-alpha levels. Infectious complications were also recorded. RESULTS One hundred twenty patients completed the study and four patients were excluded. On postoperative day 9, among patients receiving an immune enhancing diet, IgG, IgA, CD4 and CD4/CD8 levels were significantly higher and TNF-alpha and IL-6 concentrations were significantly lower compared to the control group. Moreover, among patients receiving an immune enhancing diet, when comparing preoperation to day 9 postoperation levels, increases in IgA, CD4, and CD4/CD8 levels were significantly higher than in control patients and increases in TNF-alpha concentrations were significantly lower. No statistically significant differences were found between the two groups with regard to infectious complications. CONCLUSIONS Postoperative administration of immune enhancing enteral nutrition in patients undergoing major abdominal surgery can positively modulate postoperative immunosuppressive and inflammatory responses.