Interferon-free treatment of HCV in HIV/HCV co-infected subjects results in increased serum LDL concentration.

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.