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

Florence Abravanel, Stéphanie Raymond, Elodie Pambrun, Maria Winnock, Philippe Bonnard, Philippe Sogni, Pascale Trimoulet, François Dabis, Dominique Salmon-Ceron, Jacques Izopet, ANRS CO13 HEPAVIH Study Group, F Dabis, M Winnock, M A Loko, P Sogni, Y Benhamou, P Trimoulet, J Izopet, V Paradis, B Spire, P Carrieri, C Katlama, G Pialoux, M A Valantin, P Bonnard, I Poizot-Martin, B Marchou, E Rosenthal, A Bicart-See, R Djebbar, A Gervais, C Lascoux-Combe, C Goujard, K Lacombe, C Duvivier, D Vittecoq, D Neau, P Morlat, F Bani-Sadr, L Meyer, F Boufassa, S Dominguez, B Autran, A M Roque, C Solas, H Fontaine, L Serfaty, G Chêne, D Costagliola, S Couffin-Cadiergues, D Salmon, P Sogni, B Terris, Z Makhlouf, G Dubost, F Tessier, L Gibault, F Beuvon, E Chambon, T Lazure, A Krivine, C Katlama, M A Valantin, Y Benhamou, S Dominguez, F Charlotte, S Fourati, I Poizot-Martin, O Zaegel, A Ménard, C Tamalet, G Pialoux, P Bonnard, F Bani-Sadr, P Callard, F Bendjaballah, H Assami, B Marchou, L Alric, K Barange, S Metivier, Janick Selves, F Nicot, E Rosenthal, C Pradier, J Haudebourg, M C Saint-Paul, F Rouges, R Djebbar, M Ziol, Y Baazia, M Uzan, A Bicart-See, D Garipuy, P Yéni, A Gervais, H Adle-Biassette, D Séréni, C Lascoux Combe, P Bertheau, J Duclos, P Palmer, P M Girard, K Lacombe, P Campa, D Wendum, P Cervera, J Adam, N Harchi, J F Delfraissy, C Goujard, Y Quertainmont, C Pallier, D Vittecoq, O Lortholary, C Duvivier, S Boucly, D Neau, P Morlat, I Raymond, I Louis, P Bioulac-Sage, P Trimoulet, P Pinson, D Beniken, A-S Ritleng, A Fooladi, M Azar, P Honoré, S Breau, A Joulie, M Mole, C Bolliot, F Touam, F André, G Alexandre, A Mélard, J Baume, S Gillet, J Delaune, L Dequae Merchadou, E Pambrun, A Frosch, J Cohen, G Maradan, C Taieb, F Marcellin, M Mora, C Protopopescu, C Lions, M A Loko, M Winnock, Florence Abravanel, Stéphanie Raymond, Elodie Pambrun, Maria Winnock, Philippe Bonnard, Philippe Sogni, Pascale Trimoulet, François Dabis, Dominique Salmon-Ceron, Jacques Izopet, ANRS CO13 HEPAVIH Study Group, F Dabis, M Winnock, M A Loko, P Sogni, Y Benhamou, P Trimoulet, J Izopet, V Paradis, B Spire, P Carrieri, C Katlama, G Pialoux, M A Valantin, P Bonnard, I Poizot-Martin, B Marchou, E Rosenthal, A Bicart-See, R Djebbar, A Gervais, C Lascoux-Combe, C Goujard, K Lacombe, C Duvivier, D Vittecoq, D Neau, P Morlat, F Bani-Sadr, L Meyer, F Boufassa, S Dominguez, B Autran, A M Roque, C Solas, H Fontaine, L Serfaty, G Chêne, D Costagliola, S Couffin-Cadiergues, D Salmon, P Sogni, B Terris, Z Makhlouf, G Dubost, F Tessier, L Gibault, F Beuvon, E Chambon, T Lazure, A Krivine, C Katlama, M A Valantin, Y Benhamou, S Dominguez, F Charlotte, S Fourati, I Poizot-Martin, O Zaegel, A Ménard, C Tamalet, G Pialoux, P Bonnard, F Bani-Sadr, P Callard, F Bendjaballah, H Assami, B Marchou, L Alric, K Barange, S Metivier, Janick Selves, F Nicot, E Rosenthal, C Pradier, J Haudebourg, M C Saint-Paul, F Rouges, R Djebbar, M Ziol, Y Baazia, M Uzan, A Bicart-See, D Garipuy, P Yéni, A Gervais, H Adle-Biassette, D Séréni, C Lascoux Combe, P Bertheau, J Duclos, P Palmer, P M Girard, K Lacombe, P Campa, D Wendum, P Cervera, J Adam, N Harchi, J F Delfraissy, C Goujard, Y Quertainmont, C Pallier, D Vittecoq, O Lortholary, C Duvivier, S Boucly, D Neau, P Morlat, I Raymond, I Louis, P Bioulac-Sage, P Trimoulet, P Pinson, D Beniken, A-S Ritleng, A Fooladi, M Azar, P Honoré, S Breau, A Joulie, M Mole, C Bolliot, F Touam, F André, G Alexandre, A Mélard, J Baume, S Gillet, J Delaune, L Dequae Merchadou, E Pambrun, A Frosch, J Cohen, G Maradan, C Taieb, F Marcellin, M Mora, C Protopopescu, C Lions, M A Loko, M Winnock

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.

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. HCV RNA concentrations according to…
Figure 1. HCV RNA concentrations according to HIV-1 tropism.
Figure 2. Changes in liver stiffness according…
Figure 2. Changes in liver stiffness according to HIV-1 tropism of the 34 patients in the longitudinal study (medians are indicated by bars).

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