Circulating sCD14 Is Associated with Virological Response to Pegylated-Interferon-Alpha/Ribavirin Treatment in HIV/HCV Co-Infected Patients

Abstract

ObjectivesMicrobial 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.Methods98 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 log10 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.Results71 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).ConclusionsIn 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.

T‐cell homeostasis in chronic HCV‐infected patients treated with interferon and ribavirin or an interferon‐free regimen

“…This is in agreement with a previous study (12). However, Kared et al (25) describes higher proportion of IL-7Ra + HLADR-T cells in SVR compared to non-SVR prior to treatment, and Marchetti et al (28) describes sCD14 as a predictor of early virological response in HIV/HCV co-infected patients. Thus, whether T-cell subsets and/or microbial translocation can be used as a predictor of SVR after interferon treatment must be considered questionable, and larger studies are warranted to investigate this.…”

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…Similarly, for 98 HIV/HCV coinfected patients on virologically suppressive ART, we reported increased sCD14 levels in subjects either harboring aggressive HCV genotypes (i.e., genotypes 1 to 4) or presenting with cirrhosis (129). Furthermore, Sandler et al reported that higher sCD14 levels distinguish patients with severe liver fibrosis from those with minimal fibrosis in a cohort of hepatitis B virus (HBV)/HCV-monoinfected subjects (130).…”

“…Although several factors have been associated with the response to anti-HCV therapy, the determinants of successful full-course peg-IFN-␣-ribavirin therapy are still poorly defined (133)(134)(135)(136)(137). Interestingly, increased plasma sCD14 levels have been proven to be independently associated with poor responses to anti-HCV treatment (129,130), thus suggesting an independent role of microbial translocation in the outcome of anti-HCV therapy. Contrasting data, however, were obtained for a cohort of ART-naïve HIV/ HCV-coinfected patients with high CD4 ϩ T-cell counts, for whom higher sCD14 levels were independently associated with a decreased risk of liver disease progression, defined as a time to Fibrosis 4 (Fib-4) score of Ͼ1.45 or liver-related death.…”

Antiretroviral Therapy in HIV/HCV Co-Infection Italian Consensus Workshop

“…Both Italian and European guidelines recommend that antiretroviral treatment should precede anti-HCV treatment in patients with a supposed rapid progression of HIV disease (HIV-RNA > 100,000 copies/mL or a CD4+ T-cells decay >100 cells/uL in the previous year) at any level of CD4 cell count, and in the case of CD4+ T-cell counts lower than 500 cells/uL because it may help attain a sustained virological response (SVR) [64,65]. Indeed, data from a large observational Italian study on treatment of HCV infection in HIV-infected patients seem to support an earlier start of cART in co-infected subjects undergoing standard anti-HCV treatment (based on peg Interferon and ribavirin), as suppression of HIV-RNA was significantly associated with "eradication" (SVR) of HCV infection [66].…”