Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients

Journal of Viral Hepatitis
Early View (Articles online in advance of print)
Published Online: 3 Aug 2010
© 2010 Blackwell Publishing Ltd

E. S. A. Araújo 1 , H. Dahari 2 , A. U. Neumann 3 , N. de Paula Cavalheiro 1 , C. E. Melo 1 , E. S. de Melo 1 , T. J. Layden 2 , S. J. Cotler 2 and A. A. Barone 1

1 University of São Paulo Hospital das Clínicas, São Paulo, Brazil ; 2 Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA ; and 3 Bar Ilan University, Life Sciences Faculty, Ramat Gan, Israel

Correspondence to Evaldo Stanislau Affonso de Araújo, Hospital das Clínicas da Universidade de São Paulo, Infectious Diseases Department – Hepatitis Unit-LIM 47, Av.Dr.Enéas de Carvalho Aguiar, 500 Sala 12 Cerqueira César, 05401-000 São Paulo, SP, Brazil E-mail: evaldostanislau@uol.com.br

KEYWORDS
HCV • HIV • pegylated interferon • viral kinetics

ABSTRACT

Summary. The objective of this study was to find very early viral kinetic markers to predict nonresponse to hepatitis C virus (HCV) therapy in a group of human immunodeficiency virus (HIV)/HCV-coinfected patients. Twenty-six patients (15 HCV genotype-1 and 11 genotype-3) were treated with a 48-week regimen of peginterferon-alfa-2a (PEG-IFN) (180 μg/week) and weight-based ribavirin (11 mg/kg/day). Samples were collected at baseline; 4, 8, 12, 18, 24, 30, 36 and 42 h; days 2, 3, 4, 7, 8, 15, 22, 29, 43 and 57 then weekly and monthly. Five patients discontinued treatment. Seven patients (27%) achieved a sustained virological response (SVR). Nadir HCV RNA levels were observed 1.6 ± 0.3 days after initiation of therapy, followed by a 0.3- to 12.9-fold viral rebound until the administration of the second dose of PEG-IFN, which were not associated with SVR or HCV genotype. A viral decline <1.19 log for genotype-1 and <0.97 log for genotype-3, 2 days after starting therapy, had a negative predictive value (NPV) of 100% for SVR. The day 2 virological response had a similar positive predictive value for SVR as a rapid virological response at week 4. In addition, a second-phase viral decline slope (i.e., measured from day 2 to 29) <0.3 log/week had a NPV = 100% for SVR. We conclude that first-phase viral decline at day 2 and second-phase viral decline slope (<0.3 log/week) are excellent predictors of nonresponse. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of nonresponse in patients with HCV and HIV.

Received March 2010; accepted for publication June 2010

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1365-2893.2010.01358.x About DOI
 
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