title: Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration.
abstract: 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 antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCV-monoinfected 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. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected 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-coinfected 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-coinfected subjects.
authors.affiliation: 1 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
authors.forename: Kerry
authors.initials: K
authors.lastname: Townsend
authors.affiliation: 1 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.|2 Division of Infectious Diseases, Department of Microbiology and Immunology, Medical University of South Carolina , Charleston, South Carolina.|3 Critical Care Medicine Department, NIH Clinical Center , Bethesda, Maryland.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Meissner
authors.affiliation: 3 Critical Care Medicine Department, NIH Clinical Center , Bethesda, Maryland.
authors.forename: Sreetha
authors.initials: S
authors.lastname: Sidharthan
authors.affiliation: 4 Clinical Center, Department of Laboratory Medicine, National Institutes of Health , Bethesda, Maryland.
authors.forename: Maureen
authors.initials: M
authors.lastname: Sampson
authors.affiliation: 5 Lipoprotein Metabolism Section, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: 6 Division of Infectious Diseases, Institute of Human Virology, University of Maryland , Baltimore, Maryland.
authors.forename: Lydia
authors.initials: L
authors.lastname: Tang
authors.affiliation: 3 Critical Care Medicine Department, NIH Clinical Center , Bethesda, Maryland.|7 St. Joseph's Hospital and Medical Center, Creighton University School of Medicine , Department of Hepatology, Phoenix, Arizona.
authors.forename: Anita
authors.initials: A
authors.lastname: Kohli
authors.affiliation: 2 Division of Infectious Diseases, Department of Microbiology and Immunology, Medical University of South Carolina , Charleston, South Carolina.|6 Division of Infectious Diseases, Institute of Human Virology, University of Maryland , Baltimore, Maryland.|8 Gilead Sciences Inc. , Foster City, California.
authors.forename: Anu
authors.initials: A
authors.lastname: Osinusi
authors.affiliation: 3 Critical Care Medicine Department, NIH Clinical Center , Bethesda, Maryland.
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
authors.affiliation: 1 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.|6 Division of Infectious Diseases, Institute of Human Virology, University of Maryland , Baltimore, Maryland.
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases; D008078:Cholesterol, LDL / Q000097:blood*; D060085:Coinfection / Q000188:drug therapy* / Q000821:virology; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000139:chemically induced*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D008078:Cholesterol, LDL; D005449:Fluorenes; D005663:Furans; C573362:GS-9451; C582393:GS-9669; D011804:Quinolines; D013876:Thiophenes; C000595958:ledipasvir, sofosbuvir drug combination; C586541:ledipasvir; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir