HCV Viral Decline at Week 2 of Peg-IFN-Alpha-2a/RBV Therapy as a Predictive Tool for Tailoring Treatment in HIV/HCV Genotype 1 Co-Infected Patients Antonio Rivero-Juarez 1 , Luis F. Lo ´ pez-Corte ´s 2 , Angela Camacho 1 , Almudena Torres-Cornejo 2 , Ana Gordon 1 , Rosa Ruiz-Valderas 2 , Julian Torre-Cisneros 1 , Juan A. Pineda 3 , Pompeyo Viciana 2 , Antonio Rivero 1 * 1 Unidad de Enfermedades Infecciosas, Instituto Maimonides de Investigacio ´ n Biome ´dica de Co ´ rdoba (IMIBIC), Hospital Universitario Reina Sofı ´a de Co ´ rdoba, Co ´ rdoba, Spain, 2 Unidad Clı ´nica de Enfermedades Infecciosas, Microbiologı ´a y Medicina Preventiva, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocı ´o/CSIC/Universidad de Sevilla, Seville, Spain, 3 Unidad de Enfermedades Infecciosas y Microbiologı ´a Clı ´nica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario de Valme, Seville, Spain Abstract Background: Optimizing HCV genotype 1 therapy in terms of response prediction and tailoring treatment is undoubtedly the cornerstone of treating HIV co-infected patients in clinical practice. Accordingly, our aim was to analyze the predictive value of HCV viral decline for sustained virological response (SVR), measured at a time point as early as week 2 of therapy with pegylated interferon alpha-2a plus ribavirin (Peg-IFN/RBV). Methods: Previously untreated HIV/HCV genotype 1 co-infected patients were included in this study. The HCV RNA titer was measured at week 2 after starting treatment with Peg-IFN/RBV. The likelihood of reaching SVR when HCV RNA viral titers declined at week 2 was evaluated relative to predictive baseline factors. Results: A total of 192 HIV/HCV genotype-1 co-infected patients were enrolled in the study and began therapy. One hundred and sixty-three patients completed a full course of Peg-IFN/RBV treatment for 2 weeks and 59 of these (36.2%) reached SVR. An HCV RNA viral load decline of $1.5 log IU/mL at week 2 had the maximum positive predictive value for SVR (83.3%; 95% CI: 68.5%–92.9%) and was identified as the strongest independent predictive factor for reaching SVR across all baseline predictive factors. Conclusions: HCV viral decline at week 2 had a high predictive value for identifying patients with a high and low likelihood of reaching SVR using dual therapy, regardless of strong predictive baseline factors. This finding may be useful for developing a predictive tool to help tailor HCV genotype 1 therapy in HIV co-infected patients. Citation: Rivero-Juarez A, Lo ´ pez-Corte ´ s LF, Camacho A, Torres-Cornejo A, Gordon A, et al. (2014) HCV Viral Decline at Week 2 of Peg-IFN-Alpha-2a/RBV Therapy as a Predictive Tool for Tailoring Treatment in HIV/HCV Genotype 1 Co-Infected Patients. PLoS ONE 9(6): e99468. doi:10.1371/journal.pone.0099468 Editor: Yue Wang, National Institute for Viral Disease Control and Prevention, CDC, China, China Received March 6, 2014; Accepted May 15, 2014; Published June 19, 2014 Copyright: ß 2014 Rivero-Juarez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was partly supported by grants from the Fundacio ´ n Progreso y Salud, Consejerı ´a de Salud de la Junta de Andalucı ´a (grants for health research projects; refs. 0036-2010, 0157-2011, 0430-2012). A.R. was the recipient of a research extension grant from the Fundacio ´ n Progreso y Salud, Consejerı ´a de Salud de la Junta de Andalucı ´a (ref. AI-0021). A.R.-J. is the recipient of a Post-Doctoral Research Grant from the Fundacio ´ n Progreso y Salud, Consejerı ´a de Salud de la Junta de Andalucı ´a. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: Neither the authors nor their institution have received payment or services at any time from a third party for any aspect of the submitted work (e.g., data monitoring board, study design, manuscript preparation, statistical analysis, etc.). Apart from the submitted work, A.R. and J.A.P. have received consulting fees from Bristol-Myers Squibb, Abbott, Gilead, Roche, Boehringer Ingelheim, GlaxoSmithKline, Merck Sharp & Dohme, and Janssen-Cilag. They have received lecture fees from GlaxoSmithKline, Roche, Abbott, Bristol-Myers Squibb, Boehringer Ingelheim and Schering-Plough. The remaining authors have no conflicts of interest to declare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. * Email: ariveror@gmail.com Introduction Adding a direct-acting antiviral (DAA) drug for the treatment of hepatitis C (HCV) to pegylated-interferon plus ribavirin therapy (Peg-IFN/RBV) substantially improves the sustained virological response (SVR) rate in HCV genotype 1 patients co-infected with the human immunodeficiency virus (HIV) [1]. HCV DAAs are currently available in routine clinical practice. The results obtained from using these new drugs in previously untreated co- infected HIV/HCV genotype 1 patients show significantly enhanced SVR rates in this subset of patients [1]. Nevertheless, there are several limitations to the addition of these drugs that could limit their use in those patients who are starting their first anti-HCV treatment. Perhaps the most important limitation worldwide is the substantial increase in therapy costs [2]. Therefore, even though DAAs increase the chances of reaching SVR, the use of Peg-IFN/RBV alone in HCV genotype 1 patients may remain the first-line therapeutic option in most countries according to World Health Organization (WHO) HCV treatment guidelines [1]. So, optimizing HCV genotype 1 therapy, in terms of response prediction and tailoring the treatment, is unquestion- PLOS ONE | www.plosone.org 1 June 2014 | Volume 9 | Issue 6 | e99468