A negative HCV RNA test 4 weeks into therapy is defined as a rapid virological response (RVR) and is associated AZD2281 with an increased likelihood of SVR [194,195]. The early virological response (EVR) is defined as a negative HCV RNA or reduction of >2 log10 in HCV viraemia after 12 weeks of therapy [195]. Therapy should be stopped in patients who do not achieve an EVR or where there is detectable viraemia at

24 weeks [194,195]. In the AIDS Pegasys Ribavirin International Co-infection Trial (APRICOT) study, patients treated with peginterferon and ribavirin had a mean CD4 count decrease of 140 cells/μL [196] and there have been previous case reports of interferon-treated patients developing opportunistic infections following an interferon-associated CD4 count decline. Ideally, therefore, patients should have a CD4 count of at least 200 cells/μL and undetectable HIV RNA. CD4 percentage should also be taken into account when making the treatment decision. Patients with low CD4 count (<300 cells/μL at baseline) will require more detailed monitoring. In patients being evaluated for both antiretroviral

and HCV treatment it is advisable to stabilize the patient on ART in the first instance (see above). It has been shown that the immune restoration associated with ART can limit the progression of HCV-associated disease so that even if they do not respond to HCV therapy there may be some long-term indirect benefit from ART [172,197–199]. The liver disease should also be staged both clinically and with either noninvasive tests/biomarkers such as hepatic elastography (see Navitoclax General section) or liver biopsy. Consider liver biopsy particularly for those with genotype 1 or 4 infection where the Carnitine dehydrogenase results of HCV therapy remain disappointing [198,200,201]. The risk–benefit of liver biopsy

should be considered in the individual patient. The patient’s age should also be taken into account as there is some evidence that response diminishes with increasing age [202]. It is particularly important to establish whether the patient has cirrhosis as: (a) HCV therapy can be potentially dangerous in those with severe liver disease, particularly cirrhosis Child–Pugh stage B/C, as deaths have occurred [201,203,204]. Overall, the SVR rates in coinfected patients are approximately 60% of those seen in HCV-monoinfected patients [194–196,200–202,205]. It is reasonable, therefore, to treat patients with genotype 2 or 3 infection without performing a baseline liver biopsy if there is no evidence of advanced liver disease clinically, or by using noninvasive tests/biomarkers. In those with genotype 1 or 4 infection, or where there is clinical concern regarding co-existent liver disease such as haemochromatosis, or alcohol-related or other liver disease, a biopsy can be helpful in staging the liver disease(s) and determining the need for HCV therapy [194–196,200–202,205,206].