OBJECTIVES: Microbial translocation (MT) through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients. METHODS: 98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha)/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS), host response to MT (sCD14), CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10) reduction from baseline after 12 weeks of therapy) and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy). Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR. RESULTS: 71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053) and no cirrhosis (p = 0.052). EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively), but similar T-cell activation compared to Non-EVR (Null Responders, NR) and Non-SVR (N-SVR) subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015). SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014). CONCLUSIONS: In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy
Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients / G. Marchetti, P. Nasta, F. Bai, F. Gatti, G.M. Bellistrì, C. Tincati, F. Borghi, G. Carosi, M. Puoti, A. d’Arminio Monforte. - In: PLOS ONE. - ISSN 1932-6203. - 7:2(2012 Feb 21), pp. e32028.e32028.1-e32028.e32028.12.
|Titolo:||Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients|
|Parole Chiave:||CHRONIC HEPATITIS-C ; IMMUNODEFICIENCY-VIRUS INFECTION ; T-CELL-ACTIVATION ; HIV-INFECTION ; LIVER-DISEASE ; MICROBIAL TRANSLOCATION ; IMMUNE ACTIVATION ; GENE-EXPRESSION ; ANTIRETROVIRAL THERAPY ; PREDICTIVE-VALUE|
|Settore Scientifico Disciplinare:||Settore MED/17 - Malattie Infettive|
|Data di pubblicazione:||21-feb-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0032028|
|Appare nelle tipologie:||01 - Articolo su periodico|