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. 2012;7(11):e50289.
doi: 10.1371/journal.pone.0050289. Epub 2012 Nov 30.

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

Florence Abravanel  1 , Stéphanie Raymond, Elodie Pambrun, Maria Winnock, Philippe Bonnard, Philippe Sogni, Pascale Trimoulet, François Dabis, Dominique Salmon-Ceron, Jacques Izopet; ANRS CO13 HEPAVIH Study Group
Collaborators, Affiliations

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

Florence Abravanel et al. PLoS One. 2012.

Abstract

Background and aims: Hepatic stellate cells, the major producers of extracellular matrix in the liver, and hepatocytes bear CXCR4 and CCR5, the two main co-receptors for entry of the human immunodeficiency virus (HIV). In vitro studies suggest that HIV-envelope proteins can modulate the replication of hepatitis C virus (HCV) and fibrogenesis. We investigated the influence of HIV tropism on liver fibrosis and the concentration of HCV RNA in HIV-HCV co-infected patients.

Methods: We used a phenotypic assay to assess HIV tropism in 172 HCV-HIV co-infected patients: one group (75 patients) had mild fibrosis (score ≤F2) and the other (97 patients) had severe fibrosis (score >F2). We also assessed the relationship between HIV tropism and HCV RNA concentration in all these patients. We also followed 34 of these patients for 3 years to determine the evolution of HIV tropism and liver fibrosis, estimated by liver stiffness.

Results: Initially, most patients (91.8%) received a potent antiretroviral therapy. CXCR4-using viruses were found in 29% of patients. The only factor associated with a CXCR4-using virus infection in multivariate analysis was the nadir of CD4 cells: <200/mm(3) (OR: 3.94, 95%CI: 1.39-11.14). The median HCV RNA concentrations in patients infected with R5 viruses, those with dual-mixed viruses and those with X4 viruses, were all similar. The prevalence of CXCR4-using viruses in patients with mild fibrosis (≤F2) (31%) and those with severe fibrosis (F3-F4) (28%, p = 0.6) was similar. Longitudinal analyses showed that the presence of CXCR4-using viruses did not increase the likelihood of fibrosis progression, evaluated by measuring liver stiffness.

Conclusions: The presence of CXCR4-using viruses in patients receiving a potent antiretroviral therapy does not influence HCV RNA concentration or liver fibrosis.

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Conflict of interest statement

Competing Interests: The ANRS CO13 HEPAVIH cohort is sponsored by Abbott France, Glaxo-Smith-Kline, Roche and Schering-Plough, and INSERM's “Programme cohortes TGIR.” This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. HCV RNA concentrations according to HIV-1 tropism.
Figure 2
Figure 2. Changes in liver stiffness according to HIV-1 tropism of the 34 patients in the longitudinal study (medians are indicated by bars).
See this image and copyright information in PMC

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