BACKGROUND: Hepatitis C virus (HCV) quasispecies diversity is more likely to affect early viral decline during treatment of hepatitis C than is having human immunodeficiency virus (HIV) infection. We evaluated the influence of HCV therapy on changes in the nonstructural 5A (NS5A) protein. METHODS: Fifteen patients with HCV genotype 1 infection with or without HIV infection were recruited for the present study, and the decrease in the HCV RNA level was measured at early time points. The evolution of HCV NS5A quasispecies within the first week was analyzed by comparing the clones observed at later times in the study with the baseline consensus sequence of individual patients. The response to therapy was defined as an early response (ER; ie, an HCV RNA level <615 IU/mL at week 4) or a slow response (SR; ie, a detectable HCV RNA level at week 4). RESULTS: HIV infection did not affect early viral kinetics. At baseline, lower diversity was seen in NS5A and in the amino and carboxyl termini of patients with an ER, compared with those with an SR. Rapid evolution of the NS5A genetic region occurred in patients with an ER (P = .01) but not in those with an SR (P = .73). The evolution was the result of an increase in the number of amino acid substitutions in the carboxyl region (P = .02) in patients with an ER. CONCLUSIONS: Selective pressure appears to result in more-marked changes in individuals with an ER than in those with an SR. The carboxyl terminus was subject to the most change and may be an important determinant of phenotypic resistance to interferon-based therapy.
BACKGROUND: Hepatitis C virus (HCV) quasispecies diversity is more likely to affect early viral decline during treatment of hepatitis C than is having human immunodeficiency virus (HIV) infection. We evaluated the influence of HCV therapy on changes in the nonstructural 5A (NS5A) protein. METHODS: Fifteen patients with HCV genotype 1 infection with or without HIV infection were recruited for the present study, and the decrease in the HCV RNA level was measured at early time points. The evolution of HCV NS5A quasispecies within the first week was analyzed by comparing the clones observed at later times in the study with the baseline consensus sequence of individual patients. The response to therapy was defined as an early response (ER; ie, an HCV RNA level <615 IU/mL at week 4) or a slow response (SR; ie, a detectable HCV RNA level at week 4). RESULTS: HIV infection did not affect early viral kinetics. At baseline, lower diversity was seen in NS5A and in the amino and carboxyl termini of patients with an ER, compared with those with an SR. Rapid evolution of the NS5A genetic region occurred in patients with an ER (P = .01) but not in those with an SR (P = .73). The evolution was the result of an increase in the number of amino acid substitutions in the carboxyl region (P = .02) in patients with an ER. CONCLUSIONS: Selective pressure appears to result in more-marked changes in individuals with an ER than in those with an SR. The carboxyl terminus was subject to the most change and may be an important determinant of phenotypic resistance to interferon-based therapy.
Authors: Andrew H Talal; Ruy M Ribeiro; Kimberly A Powers; Michael Grace; Constance Cullen; Musaddeq Hussain; Marianthi Markatou; Alan S Perelson Journal: Hepatology Date: 2006-05 Impact factor: 17.425
Authors: Jennifer E Layden-Almer; Ruy M Ribeiro; Thelma Wiley; Alan S Perelson; Thomas J Layden Journal: Hepatology Date: 2003-06 Impact factor: 17.425
Authors: Francesca J Torriani; Maribel Rodriguez-Torres; Jürgen K Rockstroh; Eduardo Lissen; Juan Gonzalez-García; Adriano Lazzarin; Giampiero Carosi; Joseph Sasadeusz; Christine Katlama; Julio Montaner; Hoel Sette; Sharon Passe; Jean De Pamphilis; Frank Duff; Uschi Marion Schrenk; Douglas T Dieterich Journal: N Engl J Med Date: 2004-07-29 Impact factor: 91.245
Authors: Darius Moradpour; Matthew J Evans; Rainer Gosert; Zhenghong Yuan; Hubert E Blum; Stephen P Goff; Brett D Lindenbach; Charles M Rice Journal: J Virol Date: 2004-07 Impact factor: 5.103
Authors: Chunfu Wang; Jill Pflugheber; Rhea Sumpter; Donald L Sodora; Daniel Hui; Ganes C Sen; Michael Gale Journal: J Virol Date: 2003-04 Impact factor: 5.103
Authors: Ana C G Jardim; Cíntia Bittar; Renata P A Matos; Lílian H T Yamasaki; Rafael A Silva; João R R Pinho; Roberta M Fachini; Claudia M A Carareto; Isabel M V G de Carvalho-Mello; Paula Rahal Journal: BMC Infect Dis Date: 2013-02-01 Impact factor: 3.090