Background/Aims: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver tran...Background/Aims: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients. Methods: To assess the rates of SVR and baseline predictors of failure after 48 weeks of weight-adjusted peg-IFN-α-2b/RBV in 120 patients with HCV genotype 1: 61 HCV-monoinfected, 40 HIV-coinfected and 19 LT-patients. Viral clearance was evaluated in patients completing 24 weeks of therapy (n=112, 93%). Results: SVR was significantly lower in HIV-coinfection than in HCV-monoinfection or LT (18 vs. 39 vs. 42%, P < 0.02). By multivariate analysis, HIV-coinfection (OR 3.048, 95%CI 1.133-8.196; P=0.027), baseline HCV-RNA over 800,000 IU/ml (OR 2.800; 95%CI 1.121-6.993, P=0.027) and higher AST values (OR 1.009; 95%CI 1.001-1.018; P=0.028) were significantly associated to failure. Despite similar baseline HCV load (5.67 vs. 5.75 vs. 5.90 log 10 IU/ml), HIV-coinfection showed significantly lower HCV-RNA decreases than HCV-monoinfection at weeks 4 (P=0.015), 12 (P=0.015) and 24 (P=0.0003), and than LT at weeks 12 (P=0.003) and 24 (P=0.023). 36/60 subjects (60%) reaching EVR by week 12 obtained SVR vs. 3/60 (5%) who did not. Conclusions: HIV-coin-fection was independently associated to treatment failure, and led to a significantly slower HCV-RNA clearance.展开更多
Natural killer(NK)cell-mediated antibody-dependent cellular cytotoxicity(ADCC)through CD16 plays a critical role in antihuman immunodeficiency virus(HIV)responses.1–3 CD300a is a surface receptor highly expressed on ...Natural killer(NK)cell-mediated antibody-dependent cellular cytotoxicity(ADCC)through CD16 plays a critical role in antihuman immunodeficiency virus(HIV)responses.1–3 CD300a is a surface receptor highly expressed on NK cells that has the capacity to inhibit NK cell-mediated cytotoxicity in healthy donors.4 The CD300a molecule has been related to several viral infections and is able to diminish the NK cell killing of pseudorabies-infected cells through interactions with its ligands phosphatidylserine and phosphatidylethanolamine.5 In addition,CD300a expression on B and CD4+T lymphocytes is altered during HIV-1 infection,and combined antiretroviral therapy(cART)does not restore nonpathological expression levels.5,6 However,the expression and function of CD300a on NK cells during HIV-1 infection is still unknown.We have determined the surface expression of CD300a on different NK cell subsets and the capacity of this receptor to inhibit CD16-induced NK cell effector functions in healthy and HIV-1 infected individuals.展开更多
文摘Background/Aims: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients. Methods: To assess the rates of SVR and baseline predictors of failure after 48 weeks of weight-adjusted peg-IFN-α-2b/RBV in 120 patients with HCV genotype 1: 61 HCV-monoinfected, 40 HIV-coinfected and 19 LT-patients. Viral clearance was evaluated in patients completing 24 weeks of therapy (n=112, 93%). Results: SVR was significantly lower in HIV-coinfection than in HCV-monoinfection or LT (18 vs. 39 vs. 42%, P < 0.02). By multivariate analysis, HIV-coinfection (OR 3.048, 95%CI 1.133-8.196; P=0.027), baseline HCV-RNA over 800,000 IU/ml (OR 2.800; 95%CI 1.121-6.993, P=0.027) and higher AST values (OR 1.009; 95%CI 1.001-1.018; P=0.028) were significantly associated to failure. Despite similar baseline HCV load (5.67 vs. 5.75 vs. 5.90 log 10 IU/ml), HIV-coinfection showed significantly lower HCV-RNA decreases than HCV-monoinfection at weeks 4 (P=0.015), 12 (P=0.015) and 24 (P=0.0003), and than LT at weeks 12 (P=0.003) and 24 (P=0.023). 36/60 subjects (60%) reaching EVR by week 12 obtained SVR vs. 3/60 (5%) who did not. Conclusions: HIV-coin-fection was independently associated to treatment failure, and led to a significantly slower HCV-RNA clearance.
基金supported by grants to F.B.from Instituto de Salud CarlosⅢ(ISCⅢ)-Subdirección de Evaluación y Fondo Europeo de Desarrollo Regional(FEDER)(Grant PI13/00889)Marie-Curie Actions,Career Integration Grant,European Commission(Grant CIG 631674)+5 种基金.J.V.and I.T.are recipients of a predoctoral contract funded by the Department of Education,Basque Government(PRE_2018_2_0211 and PRE_2018_1_0032)I.T.is the recipient of a fellowship from the Jesús de Gangoiti Barrera Foundation(FJGB17/003)funded by ISCIII-Contratos Sara Borrell(CD17/0128)supported by ISCIII,Spanish Health Ministry(Grant no.RD06/0006/0035,RD12/0017/0037,and RD16/0025/0019)funded by the ISCIII through the RIS(RIS C03/173,RD12/0017/0018,and RD16/0002/0006)the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluación y FEDER.
文摘Natural killer(NK)cell-mediated antibody-dependent cellular cytotoxicity(ADCC)through CD16 plays a critical role in antihuman immunodeficiency virus(HIV)responses.1–3 CD300a is a surface receptor highly expressed on NK cells that has the capacity to inhibit NK cell-mediated cytotoxicity in healthy donors.4 The CD300a molecule has been related to several viral infections and is able to diminish the NK cell killing of pseudorabies-infected cells through interactions with its ligands phosphatidylserine and phosphatidylethanolamine.5 In addition,CD300a expression on B and CD4+T lymphocytes is altered during HIV-1 infection,and combined antiretroviral therapy(cART)does not restore nonpathological expression levels.5,6 However,the expression and function of CD300a on NK cells during HIV-1 infection is still unknown.We have determined the surface expression of CD300a on different NK cell subsets and the capacity of this receptor to inhibit CD16-induced NK cell effector functions in healthy and HIV-1 infected individuals.
