HIV-HCV Coinfection: Impact of Immune Dysfunction

NCT ID: NCT00575315

Last Updated: 2014-08-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 634 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2014-08-31

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.

Conditions

HIV Infections; Hepatitis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard K Sterling, MD MSc

Role: PRINCIPAL_INVESTIGATOR

VCU

Locations

Virgnia Commonwealth University

Richmond, Virginia, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 21526398 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20728569 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18366118 (View on PubMed)

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. doi: 10.1007/s10620-007-9999-6. Epub 2007 Oct 16.

Reference Type: BACKGROUND

PMID: 17939038 (View on PubMed)

Smith JO, Sterling RK. Hepatitis C and HIV. Curr Gastroenterol Rep. 2007 Mar;9(1):83-90. doi: 10.1007/s11894-008-0025-8.

Reference Type: BACKGROUND

PMID: 17335682 (View on PubMed)

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. doi: 10.1002/hep.21178.

Reference Type: BACKGROUND

PMID: 16729309 (View on PubMed)

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. doi: 10.1111/j.1572-0241.2005.40116.x.

Reference Type: BACKGROUND

PMID: 15667488 (View on PubMed)

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. doi: 10.1002/lt.20189.

Reference Type: BACKGROUND

PMID: 15237368 (View on PubMed)

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. doi: 10.1016/s1542-3565(04)00129-6.

Reference Type: BACKGROUND

PMID: 15118983 (View on PubMed)

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. doi: 10.1097/00126334-200301010-00005.

Reference Type: BACKGROUND

PMID: 12514411 (View on PubMed)

Other Identifiers

K23-DK-066578-01

Identifier Type: -

Identifier Source: secondary_id

VCU03488

Identifier Type: -

Identifier Source: org_study_id