Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with anti-retrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease 1-4. In subjects co-infected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated 5-10. Treatment of chronic HCV infection in HIV/HCV co-infected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs) 11. We previously observed a marked increase in serum LDL-C in HCV mono-infected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol 12. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV co-infected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV co-infected subjects. No change in serum LDL-C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV co-infected subjects.

Chronic hepatitis B (CHB) is a widespread global infection and a leading cause of hepatocellular carcinoma and liver failure. Current approaches to treat CHB involve the suppression of viral replication with either interferon or nucleos(t)ide analog therapy, but neither of these approaches can reliably induce viral eradication, immunologic control or long-lived viral suppression in the absence of continued therapy. In this update, we explore the major obstacles of CHB cure and review new therapeutic strategies and drug candidates.