Both are active only against HCV genotype 1 and when combined with pegylated interferon and ribavirin have led to higher rates of success in the monoinfected population. Small clinical trials have reported

similar success rates with both boceprevir and telaprevir in the coinfected population [71–74]. Data in HCV/HIV-infected cirrhotics or in individuals who have previously failed interferon and ribavirin therapy are very limited, although small series of case reports and the early results of two ANRS studies in individuals previously failing therapy with interferon and ribavirin have been reported [75–76]. Several new agents are being studied Torin 1 mouse both in the monoinfection and coinfection setting [77]. Early reports of two alternative protease inhibitors, faldaprevir and simeprevir in combination

with PEG-IF/RBV have 3-MA solubility dmso shown high rates of RVR and EVR, comparable to monoinfection studies where these agents have been associated with higher rates of SVR than presently available PIs [78–79]. Studies of interferon-sparing approaches have commenced in the setting of HIV. Results of interferon-sparing approaches have, in the monoinfected population, shown very high rates of response with relatively short periods of treatment [80]. Treatment with boceprevir and telaprevir have the disadvantages Casein kinase 1 of requiring

co-prescribing of PEG-IFN and ribavirin, difficult dosing schedules as both must be administered three times a day (although TPV has been shown to be equally effective in monoinfection when administered twice per day); difficult toxicity profiles (anaemia, neutropenia and dysgeusia with boceprevir; and anaemia, skin rash [including the rare occurrence of Stevens–Johnson syndrome] and anal discomfort with telaprevir); multiple drug interactions (including with components of ART); and cost. Comorbidities should also be taken into account when considering the need for initiation of therapy (see Table 8.2). These include those that may be worsened by the agents being considered, for example pre-existing psychiatric conditions and blood dyscrasias, and the expected benefits associated with triple therapy should be balanced with the risks of severe adverse events in cirrhotic patients, particularly in prior null responders [81]. In such individuals expert opinion from related health care professionals should be sought and maintained throughout the treatment programme. Other comorbidities should also be taken into account as they may be influenced by the presence of HCV, for example the risks of developing cardiovascular, renal and bone disease. Not in mild, moderate or severe hepatitis.