The major risk factors for the transmission of hepatitis C virus (HCV) have been sharing needles for intravenous drug use (IDU) and receiving blood and blood products; however, recent findings suggest that HCV is being increasingly sexually transmitted, particularly among HIV-positive men who engage in high-risk, unprotected sexual behaviors with other men. Sixteen HIV-positive patients were diagnosed with sexually acquired HCV infection at a leading London HIV outpatient treatment center during 2002. All 16 patients were homosexual males with no history of IDU who had been involved in high-risk, unprotected sexual behaviors, which included active and passive anal intercourse, fisting, rimming, and oral sex. Six patients (37.5%) in the cohort spontaneously cleared HCV infection and consequently tested negative for HCV RNA. The remaining 10 patients were all started on HCV treatment, which consisted of pegylated interferon alpha-2b in combination with ribavirin. Three patients (43%) have achieved a significant reduction in HCV RNA after 12 to 24 weeks of HCV treatment. The earlier HCV seroconversion is detected and treated, the better the chance of achieving viral eradication.

c Mericitabine (RG7128) is the prodrug of a highly selective cytidine nucleoside analog inhibitor (RO5855) of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. This study evaluated the effects of combining RO5855 and ribavirin on HCV replication in the HCV subgenomic replicon by using two drug-drug interaction models. The effects of RO5855 and ribavirin on the intracellular metabolism of each compound, on interferon-stimulated gene (ISG) expression, and on the viability of hepatocyte-derived cells were also investigated. RO5855 and ribavirin had additive inhibitory activities against HCV subgenomic replicon replication in drugdrug interaction analyses. RO5855 did not affect the uptake or phosphorylation of ribavirin in primary human hepatocytes, human peripheral blood mononuclear cells, or genotype 1b (G1b) replicon cells. Similarly, ribavirin did not affect the concentrations of intracellular species derived from RO5855 in primary human hepatocytes or the formation of the triphosphorylated metabolites of RO5855. Ribavirin at concentrations of >40 M significantly reduced the viability of primary hepatocytes but not of Huh7, the G1b replicon, or interferon-cured Huh7 cells. RO5855 alone or with ribavirin did not significantly alter the viability of Huh7 or G1b replicon cells, and it did not significantly affect the viability of primary hepatocytes when it was administered alone. The viability of primary hepatocytes was reduced when they were incubated with RO5855 and ribavirin, similar to the effects of ribavirin alone. RO5855 alone or with ribavirin had no effect on ISG mRNA levels in any of the cells tested. In conclusion, RO5855 did not show any unfavorable interactions with ribavirin in human hepatocytes or an HCV subgenomic replicon system. T he treatment paradigm for chronic hepatitis C virus (HCV) infection is evolving rapidly (1). The first direct-acting antiviral agents (DAAs) for HCV, i.e., the HCV NS3/4A protease inhibitors boceprevir and telaprevir, were approved in 2011 for patients infected with HCV genotype 1 (G1) virus (1). These agents significantly increase sustained virological response (SVR) rates in patients with G1 infection but must be administered in combination with pegylated alpha interferon plus ribavirin (triple therapy) (2-7). Triple therapy with boceprevir or telaprevir also increases the adverse event burden on patients and is associated with complex drug-drug interactions that are potentially difficult to manage (2-7).When protease inhibitors were evaluated as monotherapy, resistant variants emerged rapidly and control of viral replication was lost within days (8). Moreover, when telaprevir was evaluated in combination with pegylated alpha-2a interferon but without ribavirin, treatment failure rates were unacceptably high (9). Thus, the combination of pegylated alpha interferon plus ribavirin currently remains an essential component of approved protease inhibitor-based combination regimens (1). In order to further improve convenience, safety, and SVR rates in G1-infect...

Abbreviations: ALT, alanine aminotransferase; GGT, gamma glutamyltransferase; HCV, hepatitis C virus; IFN, interferon; SVR, sustained virological response. CCR5-∆32 and IL28B polymorphisms in treatment of HCV infectionPage 4 of 24 AbstractBackground: IL28B polymorphisms strongly predict spontaneous and treatment-induced