Background In vitro, gp120 of both X4 and R5 HIV-1 strains activates human hepatic stellate cells, but if it can promote liver fibrosis in vivo is unknown. We aimed to evaluate if patients carrying X4 or R5 strains have a different liver fibrosis (LF) progression over time. Methods A total of 1,137 HIV-infected patients in ICONA cohort (21% females, 7% HCV co-infected) with an available determination of HIV-1 co-receptor tropism (CRT), a Fibrosis-4 Index for Liver Fibrosis (FIB-4) <3.25 and at least one-year follow-up were included. CRT was assessed by gp120 sequencing on plasma RNA and geno2pheno algorithm (10% false positive rate) or by Trofile. LF was assessed by means of FIB-4. LF progression was defined as an absolute score increase or a transition to higher fibrosis stratum and/or occurrence of liver-related clinical events. Results A total of 249 (22%) patients carried X4 strains, which were associated with older age, lower CD4 count, lower nadir CD4, and intravenous drug use. Overall, X4 and R5 patients had similar baseline FIB-4 scores and similar mean FIB-4 slope after a median follow-up of 35 months. There was no difference between X4 and R5 for time to LF progression (p = 0.925). Estimated risk of LF at 24 months (95% CI) after baseline in X4 and R5 was 10.6% (8.3 +/- 12.9) and 9.9% (5.9 +/- 14.0), respectively. Age, HCV co-infection, diabetes, HIV-duration, HIV-RNA> 100.000 cp/mL, antiretroviral therapy exposure were associated with LF progression at multivariate analysis. Conclusions A slight LF progression over time was observed in HIV-infected patients. No difference was demonstrated for X4 and R5 HIV-1 strains in accelerating LF evolution.

HIV-1 co-receptor tropism and liver fibrosis in HIV-infected patients / A. Saracino, A. Cozzi-Lepri, M. Shanyinde, F. Ceccherini Silberstein, S. Nozza, A. Di Biagio, G. Cassola, G. Bruno, M. Capobianchi, M. Puoti, L. Monno, A. D'Arminio Monforte. - In: PLOS ONE. - ISSN 1932-6203. - 13:1(2018 Jan 11). [10.1371/journal.pone.0190302]

HIV-1 co-receptor tropism and liver fibrosis in HIV-infected patients

A. D'Arminio Monforte
Ultimo
2018

Abstract

Background In vitro, gp120 of both X4 and R5 HIV-1 strains activates human hepatic stellate cells, but if it can promote liver fibrosis in vivo is unknown. We aimed to evaluate if patients carrying X4 or R5 strains have a different liver fibrosis (LF) progression over time. Methods A total of 1,137 HIV-infected patients in ICONA cohort (21% females, 7% HCV co-infected) with an available determination of HIV-1 co-receptor tropism (CRT), a Fibrosis-4 Index for Liver Fibrosis (FIB-4) <3.25 and at least one-year follow-up were included. CRT was assessed by gp120 sequencing on plasma RNA and geno2pheno algorithm (10% false positive rate) or by Trofile. LF was assessed by means of FIB-4. LF progression was defined as an absolute score increase or a transition to higher fibrosis stratum and/or occurrence of liver-related clinical events. Results A total of 249 (22%) patients carried X4 strains, which were associated with older age, lower CD4 count, lower nadir CD4, and intravenous drug use. Overall, X4 and R5 patients had similar baseline FIB-4 scores and similar mean FIB-4 slope after a median follow-up of 35 months. There was no difference between X4 and R5 for time to LF progression (p = 0.925). Estimated risk of LF at 24 months (95% CI) after baseline in X4 and R5 was 10.6% (8.3 +/- 12.9) and 9.9% (5.9 +/- 14.0), respectively. Age, HCV co-infection, diabetes, HIV-duration, HIV-RNA> 100.000 cp/mL, antiretroviral therapy exposure were associated with LF progression at multivariate analysis. Conclusions A slight LF progression over time was observed in HIV-infected patients. No difference was demonstrated for X4 and R5 HIV-1 strains in accelerating LF evolution.
biochemistry, genetics and molecular biology (all); agricultural and biological sciences (all)
Settore MED/17 - Malattie Infettive
11-gen-2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/547549
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