Summary and Introduction
Extrahepatic replication may have important implications for the treatment of hepatitis C virus (HCV). Our aim was to analyse the association between the presence of positive/negative strand HCV RNA in different peripheral blood cell subsets at the end of PegIFN/RBV treatment, and treatment response in HIV-coinfected patients. Thirty-four HCV-HIV coinfected patients who concluded 48 weeks of PegIFN/RBV treatment were included in the present study. Positive/negative strand HCV RNA was detected by amplification of the 5' untranslated region (5' UTR) using high-temperature RT-PCR in immunomagnetic-isolated cell subsets. Twenty-three patients (67.6%) had sustained virologic response (SVR) while 11 patients (32.4%) relapsed. The frequency of positive/negative strand HCV RNA in any cell subsets was significantly lower in patients with SVR (8.6%) compared to relapsers (63.6%) (P = 0.002). Baseline HCV viral load was statistically higher among patients who relapsed (P = 0.008), while patients with SVR had very early virologic response more frequently (P = 0.003). Multivariate analysis showed, among these three variables, that only the presence of positive/negative strand HCV RNA was independently associated with relapse [P = 0.024; OR 14 (14-137)]. In conclusion, the presence of positive/negative strand HCV RNA at the end of treatment is associated with relapse among HCV-HIV coinfected patients and might have important implications in the clinical practice.
With the introduction of highly active antiretroviral treatment (HAART), hepatitis C virus (HCV)-HIV coinfection emerged as the main cause of comorbidity, frequently associated with a faster progression of liver disease. Hence, anti-HCV treatment, currently based on pegylated-interferon-alfa and ribavirin (PegIFN/RBV), in coinfected patients is of particular importance. It has been reported an overall rate of 40% of sustained virologic response (SVR) among HCV-HIV coinfected patients, lower than the reported for HCV-monoinfected patients. Different factors have been associated with this lower treatment response, such as higher serum HCV viral load at baseline, co-treatment with antiretroviral therapy, and higher degree of immune deterioration.
HCV is a positive strand RNA virus whose replication involves the synthesis of a negative strand RNA molecule. The virus mainly replicates in hepatocytes but it can also replicate in extrahepatic reservoirs, as peripheral blood mononuclear cells (PBMCs), particularly in patients coinfected with HIV. Several studies have reported the presence of HCV RNA in PBMCs, dendritic cells, monocytes/macrophages, and B lymphocytes, although these data have to be taken with caution because most of these studies utilized different technical approaches. The detection of HCV RNA in such extrahepatic reservoirs might have important implications for transmission, disease progression, and effective treatment.
While different studies among HCV-monoinfected patients have reported the presence of HCV RNA in PBMCs in patients who had SVR, others have reported HCV RNA clearance in PBMCs as a predictor of response to antiviral therapy. Nevertheless, the association between HCV RNA in isolated peripheral blood cell subsets at the end of anti-HCV treatment and the SVR has not been previously studied in HCV-HIV coinfected patients.
Hence, the objective of our study was to analyse the association between the presence of positive/negative strand HCV RNA in different isolated cell subsets at the end of treatment (48 weeks) and SVR in HCV-HIV coinfected patients.