Pilot Study of Pioglitazone Before HCV Retreatment in HIV/HCV Genotype 1Infected Subjects With Insulin Resistance and Previous Nonresponse to Peginterferon and Ribavirin Therapy: A5239

Marks, Kristen M. MD, MS*; Kitch, Douglas MS; Chung, Raymond T. MD; Hadigan, Colleen MD, MPH§; Andersen, Janet ScD; Tien, Phyllis MD‖,¶; Luetkemeyer, Annie MD#; Alston-Smith, Beverly MD§; Glesby, Marshall J. MD, PhD*; the A5239 Team

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 March 2014 - Volume 65 - Issue 3 - p 345–349
doi: 10.1097/QAI.0000000000000073
Brief Report: Clinical Science

Abstract: Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment. In this multicenter, single-arm pilot study, adult, HIV/HCV genotype 1–coinfected previous nonresponders to peginterferon/ribavirin (PegIFN/RBV) with homeostatic model assessment of insulin resistance >2.5 were treated with pioglitazone (PIO) for 24 weeks followed by PegIFN/RBV/PIO. Three of 19 subjects (15.8%) achieved undetectable HCV RNA at week 24 of PegIFN/RBV/PIO, which was not significantly different than the historical null rate of 10% (P = 0.29, lower limit of the exact 1-sided 90% confidence interval 5.9%). Over the 24 weeks of PIO monotherapy, alanine aminotransferase and aspartate aminotransferase declined significantly and correlated with improved metabolic parameters.

*Division of Infectious Diseases, Weill Cornell Medical College, New York, NY;

Harvard School of Public Health, Boston, MA;

Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA;

§National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;

Division of Infectious Diseases, University of California San Francisco Medical School, San Francisco, CA;

Medical Service, Department of Veterans Affairs, San Francisco, CA; and

#HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, CA.

Correspondence to: Kristen M. Marks, MD, Division of Infectious Diseases, Weill Cornell Medical College, 525 East 68th Street, F24, New York, NY 10065 (e-mail: markskr@med.cornell.edu).

Presented in part at the 19th Conference on Retroviruses and Opportunistic Infections, March 5–8, 2012, Seattle, WA. Abstract 783.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

Supported by Award Number UM1AI068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health, National Institute of Dental and Craniofacial Research. This research was also supported by Roche (Genentech) and Takeda Pharmaceuticals, USA, Inc. Other grant support included 1 UM1 AI068634 and 5 U01 AI38855 to AACTG/ACTG Statistical and Data Management Center; Intramural National Institute of Allergy and Infectious Diseases support (C.H.); NIH DK078772 (R.T.C.); K24 AI078884 (M.G.), U01 AI069502 (A.L.). R.T.C. received research funding from Roche Laboratories. A.L. has received research grant support to University of California San Francisco from Bristol-Myers Squibb, Gilead, and Vertex Pharmaceuticals. M.J.G. has received research support from Pfizer to Weill Cornell Medical College and has served as a consultant to Gilead Sciences, SIGA Technologies, and Pfizer. K.M.M. has received research support to Weill Cornell Medical College from Bristol-Myers Squibb, Vertex Pharmaceuticals, Janssen Pharmaceuticals, Boehringer Ingelheim, and Gilead and has received honoraria for lectures from Boehringer Ingelheim and Bristol-Myers Squibb. Also supported in part by CTU grants, including U01 AI69419 [Cornell (Site 7804)], 5UO1 AI069502-07 [University of California San Francisco AIDS CRS (Site 801)], UM1AI069532 [New York University/NYC HHC at Bellevue Hospital Center (Site 401)], UM1 AI069511 [University of Rochester (Site 1101)], AI69501 [MetroHealth Medical Center (Site 2503)], AI 069471 [Northwestern University (A2701)], UM1-AI069503 [Virginia Commonwealth University (Site 31475)], and Massachusetts General Hospital (Site 101) CTU Grant IU0IAI69472. Also supported in part by grants funded by site CTSCs, including UL1 TR000457 (Cornell CTSC), UL1TR000439 from the National Center for Advancing Translational Sciences component of the National Institutes of Health (NIH) and NIH roadmap for Medical Research (Clinical and Translational Science Collaborative of Cleveland), UL1TR000058 from the National Center for Advancing Translational Sciences (Virginia Commonwealth University).

Received June 24, 2013

Accepted November 11, 2013

© 2014 by Lippincott Williams & Wilkins