New treatments for chronic hepatitis C

Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C

HIV infection of non-dividing cells: a divisive problem

Understanding how lentiviruses can infect terminally differentiated, non-dividing cells has proven a very complex and controversial problem. It is, however, a problem worth investigating, for it is central to HIV-1 transmission and AIDS pathogenesis. Here I shall attempt to summarise what is our current understanding for HIV-1 infection of non-dividing cells. In some cases I shall also attempt to make sense of controversies in the field and advance one or two modest proposals

HCVerso2: a phase III study of faldaprevir plus deleobuvir and ribavirin for chronic HCV genotype 1b infection in treatment naïve patients including those ineligible for pegylated interferon

peer reviewedIn treatment-naïve, non-cirrhotic patients with HCV GT1b infection, faldaprevir + deleobuvir + ribavirin for 16 or 24 w resulted in comparable SVR 12 rates (76% vs 82%) with similar tolerability profiles. Patients with cirrhosis achieved SVR 12 of 74% (24w). The adjusted SVR rates for 16 or 24w in patients with or without cirrhosis were significantly higher than historical control

Faldaprevir (BI 201335), BI 207127 and ribavirin oral therapy for treatment-naive HCV genotype 1 : SOUND-C1 final results

BACKGROUND: Faldaprevir (BI 201335) and BI 207127 are direct-acting antiviral agents under development for the treatment of chronic hepatitis C virus infection. This article describes the final results of the phase 1b SOUND-C1 study which evaluated the interferon-free oral combination of faldaprevir, BI 207127, and ribavirin in 32 treatment-naive patients infected with hepatitis C virus genotype 1. METHODS: Patients were randomized to receive BI 207127 400 mg (n=15) or 600 mg (n=17) three times daily plus faldaprevir 120 mg once daily and weight-based ribavirin for 4 weeks. Interferon-free therapy was followed by response-guided faldaprevir plus pegylated interferon alfa-2a/ribavirin to week 24 or 48. RESULTS: At week 4, 73% (11/15) and 100% (17/17) of patients in the BI 207127 400 mg and 600 mg groups achieved hepatitis C virus (HCV) RNA >25 IU/mL, respectively. During interferon-free treatment, virological breakthrough was reported in one patient and re-increase of HCV RNA in one patient. Both patients were successfully treated with interferon-containing therapy. The rate of sustained virological response 24 weeks after completion of treatment was 73% (11/15) in the BI 207127 400 mg group and 94% (16/17) in the 600 mg group. During faldaprevir plus pegylated interferon alfa-2a/ribavirin treatment, the most common adverse events were pruritus (38% of patients), rash (31%), and asthenia (31%); these were severe in approximately 3% of patients. CONCLUSIONS: Potent antiviral activity and favourable safety of the treatment regimen were demonstrated. Furthermore, the results suggest that patients with breakthrough at week 4 may be rescued with an interferon-containing regimen