In HIV/HCV coinfected patients dendritic cell activation state is not associated with IL28B genotype.

Anti-hepatitis C virus (HCV) treatment in patients infected with human immunodeficiency virus (HIV) has become a focus of recent clinical investigations. HCV treatment efficacy appears to be dependent on the patient’s immunological status at the baseline, with the response rate being directly proportional to the pretreatment CD4 cell count [1, 2]. In HCV monoinfected individuals, a strong association between allelic variants of IL28B gene encoding interferon λ3 (IFNλ3) and response to pegylated interferon alfa (peg-IFN-α) and ribavirin (RBV) treatment was reported. Failure to respond to treatment was associated with minor allele rs2979860 (T) [3]. This association has been replicated in the setting of HIV/ HCV co-infection [4], where the good response IL28B genotype was associated with higher rates of sustained virological response (SVR), compared with poorresponse variants. However, the functional role of IL28B in HCV pathogenesis and therapy outcome remains unknown. Anthony and colleagues recently reported interesting data regarding the association between soluble CD14 (sCD14) and CD16 + CD56natural killer (NK) cells with response to IFN/RBV therapy in HIV/HCV genotype 1 coinfected patients [5]. They found that baseline plasma sCD14 and CD16 + CD56NK cell frequencies were negatively associated with the magnitude of HCV load decline at weeks 4 and 24 and with SVR, suggesting that this marker of immune activation is a negative predictor of successful therapy. However, no correlation was observed between sCD14 or CD16 + CD56NK cells and IL28B genotype. Recently, we found that the baseline activation state of circulating plasmacytoid dendritic cell (pDC), from HIV/HCV coinfected patients (including genotypes 1, 2, 3, 4), correlates with therapy efficacy, including early virological response (EVR) and SVR. Moreover, IFN-α treatment induced the up-regulation of the activation state of pDC and myeloid DC (mDC) in both EVR and SVR, but not in non-EVR and non-SVR [6]. These data suggest that in HIV/HCV coinfected individuals, a high baseline maturation level of pDC may indicate their exhaustion and subsequent inability to respond to further IFN-α stimulation, confirming in these cells the impairment of IFN-α system. In the same patients we evaluated the IL28B favorable genotype (rs12979860) and observed that the favorable IL28B genotype was not correlated with HCV decline after 4 week of treatment (1.15 ± 0.3 in C/C, 1.25 ± 0.3 in C/T