Hepatitis C is a blood-borne infection caused by the hepatitis C virus (HCV). A chronic infection, which develops in most infected subjects, may lead to liver cirrhosis with ensuing liver dysfunction and liver cancer. About 30% of HIV-positive patients are coifected with HCV. The standard of care in HIV-HCV-coinfected subjects was a combination of pegylated interferon (peg-IFN)-alpha and ribavirin for 48 weeks until few months ago. The eradication of HCV was obtained in 20-55% of cases albeit with significant side effects. Further understanding of host factors that determine the effectiveness of treatment may provide diagnostic tools to distinguish patients who will be cured from those in whom treatment is likely to be futile. The aim of this thesis was to identify biomarkers and some conditions to predict outcome of combination therapy in HIV-HCV-infected patients. The parameters studied included microbial translocation markers as sCD14 and LPS, immune activation profile as CD8+CD38+, CD4+/CD8+ ratio, and in added a HAART intensification with CCR5 inhibitors, maraviroc. We showed that in HIV-HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-IFN-apha/ribavirin. Moreover, during anti-HCV therapy there is a higher immune activation by CD8+CD38+ increasing. This data could be a major factor for outcome above all in the first phases of therapy. In conclusion, we evaluated that HAART intensification with maraviroc Per concludere si è valutato come l’intensificazione della terapia HAART con maraviroc could increase T CD4+ recovery and translate in higher probability of sustained virological response in immunological non responder subjects.

FATTORI PREDITTIVI DI RISPOSTA VIROLOGICA SOSTENUTA IN PAZIENTI CON COINFEZIONE HIV-HCV TRATTATI CON PEG-INTERFERONE E RIBAVIRINA / A. Uglietti ; tutor: G. Marchetti ; coordinatore: A. D'Arminio Monforte. - : . Università degli Studi di Milano, 2014 Dec 01. ((27. ciclo, Anno Accademico 2014. [10.13130/a-uglietti_phd2014-12-01].

FATTORI PREDITTIVI DI RISPOSTA VIROLOGICA SOSTENUTA IN PAZIENTI CON COINFEZIONE HIV-HCV TRATTATI CON PEG-INTERFERONE E RIBAVIRINA

A. Uglietti
2014-12-01

Abstract

Hepatitis C is a blood-borne infection caused by the hepatitis C virus (HCV). A chronic infection, which develops in most infected subjects, may lead to liver cirrhosis with ensuing liver dysfunction and liver cancer. About 30% of HIV-positive patients are coifected with HCV. The standard of care in HIV-HCV-coinfected subjects was a combination of pegylated interferon (peg-IFN)-alpha and ribavirin for 48 weeks until few months ago. The eradication of HCV was obtained in 20-55% of cases albeit with significant side effects. Further understanding of host factors that determine the effectiveness of treatment may provide diagnostic tools to distinguish patients who will be cured from those in whom treatment is likely to be futile. The aim of this thesis was to identify biomarkers and some conditions to predict outcome of combination therapy in HIV-HCV-infected patients. The parameters studied included microbial translocation markers as sCD14 and LPS, immune activation profile as CD8+CD38+, CD4+/CD8+ ratio, and in added a HAART intensification with CCR5 inhibitors, maraviroc. We showed that in HIV-HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-IFN-apha/ribavirin. Moreover, during anti-HCV therapy there is a higher immune activation by CD8+CD38+ increasing. This data could be a major factor for outcome above all in the first phases of therapy. In conclusion, we evaluated that HAART intensification with maraviroc Per concludere si è valutato come l’intensificazione della terapia HAART con maraviroc could increase T CD4+ recovery and translate in higher probability of sustained virological response in immunological non responder subjects.
MARCHETTI, GIULIA CARLA
D'ARMINIO MONFORTE, ANTONELLA
HIV; HEPATITIS C; ANTIVIRAL THERAPY; IMMUNE ACTIVATION; SCD14; CD8+CD38+; MARAVIROC
Settore MED/17 - Malattie Infettive
FATTORI PREDITTIVI DI RISPOSTA VIROLOGICA SOSTENUTA IN PAZIENTI CON COINFEZIONE HIV-HCV TRATTATI CON PEG-INTERFERONE E RIBAVIRINA / A. Uglietti ; tutor: G. Marchetti ; coordinatore: A. D'Arminio Monforte. - : . Università degli Studi di Milano, 2014 Dec 01. ((27. ciclo, Anno Accademico 2014. [10.13130/a-uglietti_phd2014-12-01].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/245615
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