HIV-HCV Coinfection: Impact of Immune Dysfunction

Tracking Information
First Submitted Date	December 14, 2007
First Posted Date	December 18, 2007
Last Update Posted Date	August 20, 2014
Study Start Date	July 2004
Actual Primary Completion Date	August 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures; (submitted: December 17, 2007)	Changes in liver histology [ Time Frame: 5 years ]
Original Primary Outcome Measures	Same as current
Change History	Complete list of historical versions of study NCT00575315 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures; (submitted: December 17, 2007)	Assessing the effect of confounding variables on hepatic fibrosis. [ Time Frame: 5 years ]
Original Secondary Outcome Measures	Same as current
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	HIV-HCV Coinfection: Impact of Immune Dysfunction
Official Title	HIV-HCV Coinfection: Impact of Immune Dysfunction
Brief Summary	Effective therapy for human immunodeficiency virus (HIV) infection has markedly prolonged survival in infected individuals. As a result, other diseases are now becoming clinically significant. Approximately 30% of HIV infected patients are co-infected with hepatitis C virus (HCV) which is now the leading co-morbid disease in co-infected individuals. The histologic severity and natural history of HCV has been reported to be accelerated in those co-infected with HIV. It is hypothesized that 1) the severity and progression of HCV disease is related to the immune competence of the individual, 2) immune restoration associated with HIV therapy may further accelerate the progression of HCV disease which may explain the marked increase in HCV related morbidity and mortality observed in recent years, and 3) the virologic response to anti-HCV treatment is directly related to the degree of immunologic competence. The specific aims of the proposal are: 1) To obtain, through multi-disciplinary didactic teaching, the necessary skills of clinical research design, data collection, data analysis, and biostatistical methods and 2) To study the impact of HIV disease on HCV, the effect of the immune function and immune restoration during HIV therapy on the natural history of HCV, and the efficacy of HCV treatment in HIV co-infection.
Detailed Description	Approximately 30% of HIV infected patients are co-infected with hepatitis C virus (HCV) which is now the leading co-morbid disease in co-infected individuals. The histologic severity and natural history of HCV has been reported to be accelerated in those co-infected with HIV. It is hypothesized that 1) the severity and progression of HCV disease is related to the immune competence of the individual, 2) immune restoration associated with HIV therapy may further accelerate the progression of HCV disease which may explain the marked increase in HCV related morbidity and mortality observed in recent years, and 3) the virologic response to anti-HCV treatment is directly related to the degree of immunologic competence. The specific aims of the proposal are: 1) To obtain, through multi-disciplinary didactic teaching, the necessary skills of clinical research design, data collection, data analysis, and biostatistical methods and 2) To study the impact of HIV disease on HCV, the effect of the immune function and immune restoration during HIV therapy on the natural history of HCV, and the efficacy of HCV treatment in HIV co-infection.
Study Type	Observational
Study Design	Observational Model: Cohort; Time Perspective: Prospective
Target Follow-Up Duration	Not Provided
Biospecimen	Retention: Samples With DNA; Description: Sera
Sampling Method	Non-Probability Sample
Study Population	HIV-HCV Coinfection
Condition	HIV Infections; Hepatitis
Intervention	Not Provided
Study Groups/Cohorts	Not Provided
Publications *	Shah AG, Smith PG, Sterling RK. Comparison of FIB-4 and APRI in HIV-HCV coinfected patients with normal and elevated ALT. Dig Dis Sci. 2011 Oct;56(10):3038-44. doi: 10.1007/s10620-011-1710-2. Epub 2011 Apr 28.; Sterling RK, Wegelin JA, Smith PG, Stravitz RT, Luketic VA, Fuchs M, Puri P, Shiffman ML, Contos MA, Mills AS, Sanyal AJ. Similar progression of fibrosis between HIV/HCV-infected and HCV-infected patients: Analysis of paired liver biopsy samples. Clin Gastroenterol Hepatol. 2010 Dec;8(12):1070-6. doi: 10.1016/j.cgh.2010.08.004. Epub 2010 Aug 20.; Sterling RK, Contos MJ, Smith PG, Stravitz RT, Luketic VA, Fuchs M, Shiffman ML, Sanyal AJ. Steatohepatitis: Risk factors and impact on disease severity in human immunodeficiency virus/hepatitis C virus coinfection. Hepatology. 2008 Apr;47(4):1118-27. doi: 10.1002/hep.22134.; Sterling RK, Chiu S, Snider K, Nixon D. The prevalence and risk factors for abnormal liver enzymes in HIV-positive patients without hepatitis B or C coinfections. Dig Dis Sci. 2008 May;53(5):1375-82. Epub 2007 Oct 16.; Smith JO, Sterling RK. Hepatitis C and HIV. Curr Gastroenterol Rep. 2007 Mar;9(1):83-90. Review.; Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006 Jun;43(6):1317-25.; Sterling RK, Brown RS Jr, Hofmann CM, Luketic VA, Stravitz RT, Sanyal AJ, Contos MJ, Mills AS, Smith V, Shiffman ML. The spectrum of chronic hepatitis C virus infection in the Virginia Correctional System: development of a strategy for the evaluation and treatment of inmates with HCV. Am J Gastroenterol. 2005 Feb;100(2):313-21.; Stravitz RT, Shiffman ML, Sanyal AJ, Luketic VA, Sterling RK, Heuman DM, Ashworth A, Mills AS, Contos M, Cotterell AH, Maluf D, Posner MP, Fisher RA. Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation. Liver Transpl. 2004 Jul;10(7):850-8.; Sterling RK, Wilson MS, Sanyal AJ, Luketic VA, Stravitz RT, Contos MJ, Mills AS, Shiffman ML. Impact of highly active antiretroviral therapy on the spectrum of liver disease in HCV-HIV coinfection. Clin Gastroenterol Hepatol. 2004 May;2(5):432-9.; Sterling RK, Contos MJ, Sanyal AJ, Luketic VA, Stravitz RT, Wilson MS, Mills AS, Shiffman ML. The clinical spectrum of hepatitis C virus in HIV coinfection. J Acquir Immune Defic Syndr. 2003 Jan 1;32(1):30-7.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status	Completed
Actual Enrollment; (submitted: August 19, 2014)	634
Original Estimated Enrollment; (submitted: December 17, 2007)	400
Actual Study Completion Date	August 2014
Actual Primary Completion Date	August 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria	Inclusion Criteria: HIV antibody positive; Positive HCV-RNA; Age > 18 years Exclusion Criteria: Coagulopathy (prothrombin time prolonged > 2 seconds from control); Presence of ascites; Thrombocytopenia (platelet < 70,000); Active or recent (within 3 months) opportunistic infection related to HIV; Advanced HIV disease with life expectancy less than 1 year; Renal failure; Hepatitis B surface antigen positive; Inability to give informed consent
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 90 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	United States
Removed Location Countries
Administrative Information
NCT Number	NCT00575315
Other Study ID Numbers	VCU03488; K23-DK-066578-01
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Virginia Commonwealth University
Study Sponsor	Virginia Commonwealth University
Collaborators	Not Provided
Investigators	Principal Investigator: Richard K Sterling, MD MSc VCU
PRS Account	Virginia Commonwealth University
Verification Date	August 2014