Impact of antiretroviral therapy on the variability of the HCV NS5B polymerase in HIV/HCV co-infected patients

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Abstract
Assessment of the impact of antiretroviral drugs on the variability of hepatitis C virus (HCV) NS5B polymerase in HIV/HCV co-infected individuals. HCV NS5B polymerase was sequenced from plasma at baseline and at the end of follow-up in HIV/HCV co-infected individuals on a stable antiretroviral regimen seen at two outpatient clinics for at least 2 years. The presence of mutations associated with drug resistance to experimental HCV polymerase inhibitors was examined. Sixty-one HIV/HCV co-infected patients (34% HCV-1a, 25% HCV-1b, 18% HCV-3 and 23% HCV-4) were analysed. The mean time on antiretroviral therapy was 52 months. All patients received HIV nucleoside analogues; 66% along with non-nucleoside analogues. The median HCV RNA was 6.1 log at baseline and 6 log IU/mL at the end of follow-up. The median HIV RNA was 4.4 log at baseline and 1.5 log copies/mL at the end of follow-up. No evidence of selection of NS5B polymerase inhibitor resistance mutations was seen when comparing samples collected at baseline and at the end of follow-up from the same individuals. All NS5B sequences from HCV-1a and HCV-3 showed V499A, associated with resistance to HCV non-nucleoside site-1 inhibitors (NNI-1). In addition, HCV-3 showed I482L, associated with resistance to NNI-2, and HCV-4 showed M414L, I482L and V499A, associated with resistance to NNI-3, 2 and 1, respectively. Two HCV-1b patients showed C316N, related with resistance to NNI-4. The use of antiretroviral drugs does not increase the rate of primary drug resistance mutations to HCV NS5B polymerase inhibitors in HIV/HCV co-infected patients. However, natural polymorphisms associated with reduced susceptibility to some HCV NNIs are common, particularly in HCV variants other than HCV-1b.

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