Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients

Summary

This study will evaluate the safety and effectiveness of combination therapy with peginterferon alfa-2b and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. In studies of patients with hepatitis C alone, interferon alfa-2b plus ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon alfa-2b is a compound that results from attaching a polyethylene glycol molecule to interferon alfa-2b. This compound stays in the blood longer than unmodified interferon alfa-2b, causing a higher blood concentration and thus maintaining activity against the hepatitis C virus. HIV-infected patients 21 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2 1/2-year study. Candidates will be screened with blood and urine tests and possibly a liver biopsy, if a recent one is not available. The liver biopsy is done to determine the severity of liver disease. For this test, patients are admitted to the NIH Clinical Center for 1 to 2 days. A sedative is injected into an arm vein, the skin in the area over the biopsy site is numbed with a local anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. A chest X-ray, electrocardiogram (EKG) and liver ultrasound are also done. Within 4 weeks of the screening tests, candidates who appear eligible for the study will have a physical examination, medical history and repeat blood tests. Women who can become pregnant will have serial pregnancy tests throughout the study. Patients who meet the study criteria and decide to participate will begin treatment with weekly injections under the skin of peginterferon alfa-2b and take ribavirin pills twice a day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Clinic visits will be scheduled as follows: * Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV. * Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56 and 64 - Blood and urine tests will be done to determine the side effects of treatment and its effect on the HCV infection. * Week 48 or end of treatment - Treatment will stop after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients will return to the clinic for a routine test.

Timeline

Start

2001-06

Primary completion

2009-04

Completion

2009-04

Publications

• Results Rozenberg L, Haagmans BL, Neumann AU, Chen G, McLaughlin M, Levy-Drummer RS, Masur H, Dewar RL, Ferenci P, Silva M, Viola MS, Polis MA, Kottilil S. Therapeutic response to peg-IFN-alpha-2b and ribavirin in HIV/HCV co-infected African-American and Caucasian patients as a function of HCV viral kinetics and interferon pharmacodynamics. AIDS. 2009 Nov 27;23(18):2439-50. doi: 10.1097/QAD.0b013e32832ff1c0.
• Results Avidan NU, Goldstein D, Rozenberg L, McLaughlin M, Ferenci P, Masur H, Buti M, Fauci AS, Polis MA, Kottilil S. Hepatitis C viral kinetics during treatment with peg IFN-alpha-2b in HIV/HCV coinfected patients as a function of baseline CD4+ T-cell counts. J Acquir Immune Defic Syndr. 2009 Dec 1;52(4):452-8. doi: 10.1097/QAI.0b013e3181be7249.
• Results Allison RD, Katsounas A, Koziol DE, Kleiner DE, Alter HJ, Lempicki RA, Wood B, Yang J, Fullmer B, Cortez KJ, Polis MA, Kottilil S. Association of interleukin-15-induced peripheral immune activation with hepatic stellate cell activation in persons coinfected with hepatitis C virus and HIV. J Infect Dis. 2009 Aug 15;200(4):619-23. doi: 10.1086/600107.
• Results Nussenblatt V, McLaughlin M, Rehm CA, Lempicki RA, Brann T, Yang J, Proschan M, Highbarger HC, Dewar RL, Imamichi T, Koratich C, Neumann AU, Masur H, Polis MA, Kottilil S. Immunodeficiency and intrinsic IFN resistance are associated with viral breakthrough to HCV therapy in HIV-coinfected patients. AIDS Res Hum Retroviruses. 2007 Nov;23(11):1354-9. doi: 10.1089/aid.2007.0091.
• Results Neumann A, Polis M, Rozenberg L, Jackson J, Reitano K, McLaughlin M, Koratich C, Dewar R, Masur H, Haagmans B, Kottilil S. Differential antiviral effect of PEG-interferon-alpha-2b on HIV and HCV in the treatment of HIV/HCV co-infected patients. AIDS. 2007 Sep 12;21(14):1855-65. doi: 10.1097/QAD.0b013e32825eaba7.
• Results Wu L, Kottilil S, Lempicki R, Yang J, McLaughlin M, Hu Z, Koratich C, Reitano KN, Rehm CA, Masur H, Wood B, Kleiner DE, Polis MA. Hepatic histologic response (HR) to combination therapy among HCV/HIV-coinfected individuals: interferon induces HR independent of sustained virologic response (SVR). AIDS Res Hum Retroviruses. 2006 Nov;22(11):1091-8. doi: 10.1089/aid.2006.22.1091.
• Results Pau AK, McLaughlin MM, Hu Z, Agyemang AF, Polis MA, Kottilil S. Predictors for hematopoietic growth factors use in HIV/HCV-coinfected patients treated with peginterferon alfa 2b and ribavirin. AIDS Patient Care STDS. 2006 Sep;20(9):612-9. doi: 10.1089/apc.2006.20.612.
• Results Farel C, Suzman DL, McLaughlin M, Campbell C, Koratich C, Masur H, Metcalf JA, Robinson MR, Polis MA, Kottilil S. Serious ophthalmic pathology compromising vision in HCV/HIV co-infected patients treated with peginterferon alpha-2b and ribavirin. AIDS. 2004 Sep 3;18(13):1805-9. doi: 10.1097/00002030-200409030-00009.
• Results Lempicki RA, Polis MA, Yang J, McLaughlin M, Koratich C, Huang DW, Fullmer B, Wu L, Rehm CA, Masur H, Lane HC, Sherman KE, Fauci AS, Kottilil S. Gene expression profiles in hepatitis C virus (HCV) and HIV coinfection: class prediction analyses before treatment predict the outcome of anti-HCV therapy among HIV-coinfected persons. J Infect Dis. 2006 Apr 15;193(8):1172-7. doi: 10.1086/501365. Epub 2006 Mar 13.
• Results Sidique N, Kohli A, Shivakumar B, Migueles S, Subramanian GM, Naggie S, Polis MA, Masur H, Kottilil S. HIV/HCV-coinfected natural viral suppressors have better virologic responses to PEG-IFN and ribavirin than ARV-treated HIV/HCV patients. J Acquir Immune Defic Syndr. 2011 Oct 1;58(2):e38-40. doi: 10.1097/QAI.0b013e31822d463f. No abstract available.
• Results Naggie S, Osinusi A, Katsounas A, Lempicki R, Herrmann E, Thompson AJ, Clark PJ, Patel K, Muir AJ, McHutchison JG, Schlaak JF, Trippler M, Shivakumar B, Masur H, Polis MA, Kottilil S. Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: impaired viral kinetics and therapeutic response. Hepatology. 2012 Aug;56(2):444-54. doi: 10.1002/hep.25647. Epub 2012 Jul 2.
• Results Osinusi A, Naggie S, Poonia S, Trippler M, Hu Z, Funk E, Schlaak J, Fishbein D, Masur H, Polis M, Kottilil S. ITPA gene polymorphisms significantly affect hemoglobin decline and treatment outcomes in patients coinfected with HIV and HCV. J Med Virol. 2012 Jul;84(7):1106-14. doi: 10.1002/jmv.23302.
• Results Burbelo PD, Kovacs JA, Ching KH, Issa AT, Iadarola MJ, Murphy AA, Schlaak JF, Masur H, Polis MA, Kottilil S. Proteome-wide anti-hepatitis C virus (HCV) and anti-HIV antibody profiling for predicting and monitoring the response to HCV therapy in HIV-coinfected patients. J Infect Dis. 2010 Sep 15;202(6):894-8. doi: 10.1086/655780.
• Results Chary A, Winters MA, Kottilil S, Murphy AA, Polis MA, Holodniy M. Impact of interferon-ribavirin treatment on hepatitis C virus (HCV) protease quasispecies diversity in HIV- and HCV-coinfected patients. J Infect Dis. 2010 Sep 15;202(6):889-93. doi: 10.1086/655784.

Drugs

Indications