Mark S. Sulkowski, MD; Kenneth E. Sherman, MD, PhD; Douglas T. Dieterich, MD; Mohammad Bsharat, PhD; Lisa Mahnke, MD, PhD; Jürgen K. Rockstroh, MD; Shahin Gharakhanian, MD, DPH; Scott McCallister, MD; Joshua Henshaw, PhD; Pierre-Marie Girard, MD, PhD; Bambang Adiwijaya, PhD; Varun Garg, PhD; Raymond A. Rubin, MD; Nathalie Adda, MD; Vincent Soriano, MD, PhD
Acknowledgment: The authors thank the coordinators, nurses, and patients involved in the study; Theorem Clinical Research, Oracle Health Sciences Global Business Unit, i3 Research and i3 Global, Covance Laboratories, Quest Pharmaceuticals, and ICON Central Laboratories for coordinating and implementing various aspects of the study; Christina (Tina) Karunaratne for clinical project management; Eileen Zhang, PhD, for virology analyses; Min Chen, MS, for statistical programming; Yang Dai, PhD, for pharmacokinetic data analysis; Jonathan Kirk for graphic design support; Leslie Lescale-Matys, PhD, for study conduct and data analysis; and Kristin Stephan, PhD, Frances Smith, PhD, Karen Eisenhauer, PhD, and Mrudula Donepudi, PhD, for medical writing and editorial assistance (all from Vertex Pharmaceuticals). The authors also thank the site investigators (see Appendix 1).
Grant Support: By the National Institute on Drug Abuse (K24DA034621 and R01DA16065), National Institute of Allergy and Infectious Diseases (P30AI094189), National Center for Research Resources and the National Institutes of Health Roadmap for Medical Research (UL1RR025005), National Institute of Diabetes and Digestive Kidney Diseases (K24 DK070528), Hickey Foundation–HONE Project (GCO 09-0395), and the National Institute of Mental Health (R34 MH099930-01A1). Funding was also provided by the Fundación Investigación y Educación en SIDA, European AIDS Treatment Network (LSHM-CT-2006-037570), European Community's Seventh Framework Program FP7/2007-2013 Collaborative HIV and Anti-HIV Drug Resistance Network (Project 223131), and Red de Investigación en SIDA (ISCIII-RETIC-RD12/0017/0031).
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0291.
Reproducible Research Statement: Study protocol: Available from Dr. Rubin (e-mail, firstname.lastname@example.org). Statistical code and data set: Not available.
Requests for Single Reprints: Mark S. Sulkowski, MD, Johns Hopkins University School of Medicine, 600 North Wolfe Street, 1830 Building, Room 445, Baltimore, MD 21287; e-mail, email@example.com.
Current Author Addresses: Dr. Sulkowski: Johns Hopkins University School of Medicine, 600 North Wolfe Street, 1830 Building, Room 445, Baltimore, MD 21287.
Dr. Sherman: University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267.
Dr. Dieterich: Mount Sinai School of Medicine, 1468 Madison Avenue, Annenberg 21-42, New York, NY, 10029.
Drs. Bsharat, Mahnke, Garg, and Rubin: Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, MA, 02139.
Dr. Rockstroh: Department of Medicine I, Universitätsklinikum Bonn, Siegmund-Freudstr. 25, 53105 Bonn, Germany.
Dr. Gharakhanian: Cambridge Innovation Center, One Broadway, 14th Floor, Cambridge, MA 02142.
Dr. McCallister: Gilead Sciences, 333 Lakeside Drive (300-132084), Foster City, CA 94404.
Dr. Henshaw: 616 Vernon Way, Burlingame, CA 94010.
Dr. Girard: Service des Maladies Infectieuses, Hôpital St. Antoine, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, France.
Dr. Adiwijaya: 16 Brighton Street, Belmont, MA 02478.
Dr. Adda: Transgene, 5 Cambridge Center, Cambridge, MA 02142.
Dr. Soriano: Department of Infectious Diseases, Hospital Carlos III, Calle Sinesio Delgado 10, Madrid 28029, Spain.
Author Contributions: Conception and design: M.S. Sulkowski, D.T. Dieterich, S. Gharakhanian, S. McCallister, P.M. Girard, V. Garg, N. Adda.
Analysis and interpretation of data: M.S. Sulkowski, K.E. Sherman, D.T. Dieterich, M. Bsharat, L. Mahnke, S. Gharakhanian, S. McCallister, J. Henshaw, B. Adiwijaya, V. Garg, R.A. Rubin, N. Adda, V. Soriano.
Drafting of the article: M.S. Sulkowski, K.E. Sherman, D.T. Dieterich, L. Mahnke, S. McCallister, P.M. Girard, V. Soriano.
Critical revision of the article for important intellectual content: M.S. Sulkowski, D.T. Dieterich, J.K. Rockstroh, S. Gharakhanian, S. McCallister, J. Henshaw, P.M. Girard, R.A. Rubin, N. Adda, V. Soriano.
Final approval of the article: M.S. Sulkowski, K.E. Sherman, D.T. Dieterich, L. Mahnke, J.K. Rockstroh, S. Gharakhanian, S. McCallister, J. Henshaw, P.M. Girard, V. Garg, R.A. Rubin, N. Adda, V. Soriano.
Provision of study materials or patients: M.S. Sulkowski, K.E. Sherman, D.T. Dieterich, J.K. Rockstroh, P.M. Girard.
Statistical expertise: M. Bsharat, B. Adiwijaya.
Administrative, technical, or logistic support: B. Adiwijaya.
Collection and assembly of data: M.S. Sulkowski, D.T. Dieterich, L. Mahnke, S. McCallister, P.M. Girard, R.A. Rubin, N. Adda, V. Soriano.
Telaprevir (TVR) plus peginterferon-α2a (PEG-IFN-α2a) and ribavirin substantially increases treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection versus PEG-IFN-α2a–ribavirin alone. Its safety and efficacy in patients with HCV and HIV-1 are unknown.
To assess the safety and efficacy of TVR plus PEG-IFN-α2a–ribavirin in patients with genotype 1 HCV and HIV-1 and to evaluate pharmacokinetics of TVR and antiretrovirals during coadministration.
Phase 2a, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT00983853)
16 international multicenter sites.
62 patients with HCV genotype 1 and HIV-1 who were HCV treatment–naive and receiving 0 or 1 of 2 antiretroviral regimens were randomly assigned to TVR plus PEG-IFN-α2a–ribavirin or placebo plus PEG-IFN-α2a–ribavirin for 12 weeks, plus 36 weeks of PEG-IFN-α2a–ribavirin.
HCV RNA concentrations.
Pruritus, headache, nausea, rash, and dizziness were higher with TVR plus PEG-IFN-α2a–ribavirin during the first 12 weeks. During this period, serious adverse events occurred in 5% (2 in 38) of those receiving TVR plus PEG-IFN-α2a–ribavirin and 0% (0 in 22) of those receiving placebo plus PEG-IFN-α2a–ribavirin; the same number in both groups discontinued treatment due to adverse events. Sustained virologic response occurred in 74% (28 in 38) of patients receiving TVR plus PEG-IFN-α2a–ribavirin and 45% (10 in 22) of patients receiving placebo plus PEG-IFN-α2a–ribavirin. Rapid HCV suppression was seen with TVR plus PEG-IFN-α2a–ribavirin (68% [26 in 38 patients] vs. 0% [0 in 22 patients] undetectable HCV RNA levels by week 4). Two patients had on-treatment HCV breakthrough with TVR-resistant variants. Patients treated with antiretroviral drugs had no HIV breakthroughs; antiretroviral exposure was not substantially modified by TVR.
Small sample size and appreciable dropout rate.
In patients with HCV and HIV-1, more adverse events occurred with TVR versus placebo plus PEG-IFN-α2a–ribavirin; these were similar in nature and severity to those in patients with HCV treated with TVR. With or without concomitant antiretrovirals, sustained virologic response rates were higher in patients treated with TVR versus placebo plus PEG-IFN-α2a–ribavirin.
Vertex Pharmaceuticals and Janssen Pharmaceuticals.
Mark S. Sulkowski, Kenneth E. Sherman, Douglas T. Dieterich, Mohammad Bsharat, Lisa Mahnke, Jürgen K. Rockstroh, et al. Combination Therapy With Telaprevir for Chronic Hepatitis C Virus Genotype 1 Infection in Patients With HIV: A Randomized Trial. Ann Intern Med. 2013;159:86–96. doi: 10.7326/0003-4819-159-2-201307160-00654
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Published: Ann Intern Med. 2013;159(2):86-96.
Gastroenterology/Hepatology, HIV, Infectious Disease, Liver Disease, Viral Hepatitis.
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