Impact of Hepatitis C Viral Clearance on CD4 + T-Lymphocyte Course in HIV/HCV-Coinfected Patients Treated with Pegylated Interferon Plus Ribavirin
Department of Clinical Sciences, Section of Infectious Diseases and Immunopathology L. Sacco, Università degli Studi di Milano, L. Sacco Hospital, Milan, Italy. AIDS research and human retroviruses
(Impact Factor: 2.33).
01/2012; 28(9):989-93. DOI: 10.1089/AID.2011.0323
The long-term impact of pegylated-interferon plus ribavirin (Peg-IFN-RBV) treatment outcome on CD4 T cell course in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is unknown. The aim of this study was to investigate the impact of HCV-RNA clearance by standard anti-HCV therapy on long-term CD4 cells recovery in HIV/HCV patients on successful combined antiretroviral therapy (cART). We retrospectively enrolled HIV/HCV-coinfected patients on stable cART, treated with Peg-IFN-RBV between 2005 and 2009. CD4(+) T cell counts were registered at baseline (pre-Peg-IFN-RBV), after 6, 12, and 24 months of follow-up from therapy discontinuation. Multiple linear regression analysis was performed to identify independent predictors of CD4(+) T cell change following the anti-HCV treatment outcome. Of the 116 patients enrolled, 54 (46.6%) reached a sustained virological response (SVR) and 62 (53.4%) did not. Throughout a median follow-up of 24 months, the SVR group showed a mean annual increase in CD4(+) T cell from baseline of 84 cells/μl at 1 year and of a further 38 cells/μl within the second year (p=0.01, 0.001, respectively). A nonsignificant mean increase of 77 cells/μl occurred in the non-SVR group within month 24 (p=0.06). Variables associated with greater CD4 gains were higher nadir and lower pre-interferon CD4 counts, and lower body mass index (BMI). The achievement of SVR was not significantly associated with the change in CD4(+) count. The clearance of HCV replication did not affect the CD4(+) changes after Peg-IFN-RBV therapy in coinfected patients on efficient cART. Liver fibrosis and higher BMI were negative determinants of immune recovery.
Available from: Rohit Talwani
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ABSTRACT: We have established a cohort of natural viral suppressors (NVS) who can suppress HIV-1 replication to less than 400 copies/ml in the absence of therapy (similar to Elite Controllers/Elite Suppressors). Of the 59 patients currently in the NVS cohort, 45.8% have chronic hepatitis C virus (HCV) infection, thereby presenting a unique opportunity to study immune activation and the interaction between HCV and HIV. NVS with chronic HCV infection had elevated levels of immune activation (CD38-positive HLA-DR-positive CD8 cells) compared to NVS without chronic HCV (P = 0.004). The increased levels of immune activation were not associated with sex, HLA B57 status, or injection drug use use. NVS patients with chronic HCV had lower mean CD4 cell counts, CD4 percentage, and CD4/CD8 ratios than NVS without chronic HCV infection (P = 0.038, P = 0.008, and P = 0.048, respectively). The difference in CD4 cell count appeared to occur early in HIV infection with no difference observed in CD4 slopes between groups. Among all NVS, there was a direct correlation between mean CD4 cell count, mean CD4 percentage, and mean CD4/CD8 ratio with percentage of CD38 HLA-DR CD8 cells (P = 0.0018; P = 0.0069; and P = 0.0014, respectively). This study suggests a relationship between HCV infection, immune activation, and CD4 cell counts in the NVS, with chronic HCV infection associated with lower CD4 cell counts and higher levels of immune activation. Further studies are needed to determine if successful HCV treatment lowers immune activation levels and/or increases CD4 cell counts in these patients.
AIDS (London, England) 07/2012; 26(15):1879-84. DOI:10.1097/QAD.0b013e328357f5d1 · 5.55 Impact Factor
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ABSTRACT: Despite suppressive combination antiretroviral therapy, a considerable proportion of HIV-infected patients do not achieve adequate immune recovery in terms of the CD4+ T-cell count, although they have controlled viremia values. Many questions remain for clinicians in the management of these patients, defined as immunological nonresponders, including questions about the mechanisms underlying the lack of immune restoration and possible therapeutic approaches to this particular group of patients.
Future Virology 09/2012; 7(9):911-921. DOI:10.2217/fvl.12.80 · 1.01 Impact Factor
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ABSTRACT: HIV/hepatitis C virus (HCV)-coinfected patients have accelerated liver disease compared with HCV monoinfection. In HIV-positive patients with viral suppression, data comparing inflammatory cytokines and immune activation between HIV/HCV coinfection with chronic hepatitis C (CHC) to HIV/HCV-seropositive patients with cleared HCV are limited.
Fifty-nine age- and sex-matched patients were stratified: (1) HIV monoinfection (n = 15); (2) HCV monoinfection with CHC (n = 15); (3) HIV/HCV coinfection with CHC (n = 14); and (4) HIV/HCV seropositive with cleared HCV (n = 15). All HIV-positive patients had undetectable HIV viremia, and median CD4 was 420 cells per microliter. Liver fibrosis was assessed in each subject using transient elastography. Cells were collected for CD4 and CD8 immune activation (CD38/HLA-DR) markers via flow cytometry and plasma for luminex-multiplex cytokine assays.
CD38HLA-DR expression on CD4 T cells was significantly increased in HIV/HCV coinfection with CHC (7%) versus HCV monoinfection (4%) (P = 0.012). CD4 total HLA-DR expression was significantly increased in HIV/HCV coinfection with CHC (43%) versus HIV monoinfection (31%) (P = 0.010) and HIV/HCV seropositive with cleared HCV (38%) (P = 0.046). Total CD4CD38 and CD4CD38HLA-DR expression was significantly higher in HIV monoinfection (23% and 18%) than HCV moninfection (13%, P = 0.002% and 9%, P = 0.001, respectively). Interleukin 10 levels were significantly lower in HIV monoinfection versus HIV/HCV coinfection with CHC (P = 0.0002). In multivariate analysis, severe fibrosis was associated with lower expression of CD4CD38HLA-DR and CD4 total CD38 than mild-moderate fibrosis (P = 0.03 and 0.03, respectively).
CD4 immune activation with HLA-DR expression in HIV/HCV coinfection with well-controlled HIV may arise from chronic HCV viremia. Conversely, CD4CD38 expression may be driven by underlying HIV infection. CD4 immune activation was unexpectedly found to be associated with decreased liver fibrosis.
JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2013; 64(3):232-240. DOI:10.1097/QAI.0b013e31829c6de0 · 4.56 Impact Factor
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