Effects of Anti-HIV Drugs on the Hepatitis C Virus (HCV) in Adults Infected With Both HCV and HIV

NCT00545558 | Completed Phase 1

• 2 other identifiers: 5R01AI065256-015R01AI065256
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to measure the effects of anti-HIV drugs on hepatitis C virus (HCV) viral load in people infected with both HCV and HIV.

Conditions

Hepatitis C; HIV Infections

Keywords

Antiretroviral Therapy, Highly Active; Coinfection; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• Underlying patterns of liver injury and hepatitis C virus (HCV) viral changes after antiretroviral therapy (ART) initiation

  Throughout study

Study Arms (1)

1

EXPERIMENTAL

Participants will receive ART consisting of efavirenz and the co-formulation of emtricitabine and tenofovir disoproxil fumarate. If participants are unable to tolerate the treatment, a different regimen will be prescribed.

Drug: Efavirenz; Drug: Emtricitabine/Tenofovir disoproxil fumarate

Interventions

Efavirenz DRUG

600 mg tablet taken orally daily

1

Emtricitabine/Tenofovir disoproxil fumarate DRUG

200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally daily

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HCV-infected
• HIV-infected
• Liver biopsy consistent with chronic hepatitis within 1 year of study entry.
• ART-naive or no ART for at least 3 months prior to study entry

You may not qualify if:

• Hemoglobin less than 9 g/dl.
• Hepatitis B virus infected or antibody to hepatitis B core antigen, alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, autoimmune disorder, or other concurrent liver disease
• Decompensated liver disease evidenced by active or history of encephalopathy, ascites, or variceal bleeding; prothrombin time (PT) greater than 3 seconds above normal or international normalized ratio (INR) greater than 1.3 sec; platelet count less than 90,000 K/ul. Participants with cirrhosis will not be excluded.
• Active thyroid disease. Participants on thyroid replacement therapy with normal thyroid-stimulating hormone are not excluded.
• Chronic kidney insufficiency, defined as creatinine clearance of greater than approximately 50 ml/min
• Life-threatening disease processes other than HIV or HCV that could interfere with participation in the study
• Any condition that, in the opinion of the investigator, may interfere with completion of the study regimen. This includes severe psychiatric disorders, or active alcohol or recreational drug abuse
• Use of systemic corticosteroids or immunomodulatory drugs within 1 month prior to study entry
• Current or prior successful interferon treatment
• Pregnancy or breastfeeding

Sponsors & Collaborators

• University of Cincinnati: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

General Clinical Research Center (GCRC), OH site

Cincinnati, Ohio, 45229, United States

Location

Virginia Commonwealth University, School of Medicine

Richmond, Virginia, 23298, United States

Location

Related Publications (10)

• Shudo E, Ribeiro RM, Perelson AS. Modelling hepatitis C virus kinetics during treatment with pegylated interferon alpha-2b: errors in the estimation of viral kinetic parameters. J Viral Hepat. 2008 May;15(5):357-62. doi: 10.1111/j.1365-2893.2007.00954.x.

  PMID: 18380660 BACKGROUND

• Shudo E, Ribeiro RM, Perelson AS. Modelling the kinetics of hepatitis C virus RNA decline over 4 weeks of treatment with pegylated interferon alpha-2b. J Viral Hepat. 2008 May;15(5):379-82. doi: 10.1111/j.1365-2893.2008.00977.x. Epub 2008 Feb 11.

  PMID: 18266841 BACKGROUND

• Blackard JT, Sherman KE. HCV/ HIV co-infection: time to re-evaluate the role of HIV in the liver? J Viral Hepat. 2008 May;15(5):323-30. doi: 10.1111/j.1365-2893.2008.00970.x. Epub 2008 Jan 17.

  PMID: 18208497 BACKGROUND

• Ma G, Barrett A, Sherman KE, Shata T, Blackard J. Detection of HIV in Liver Biopsies and Intrahepatic Lymphocytes. 15th Conference on Retroviruses and Opportunistic Infections. Boston, MA February 2008

  BACKGROUND

• Sherman KE, Rouster S, Feinberg J, Bini E, Blackard J, Shata T. Hepatic Apoptosis following Initiation of ART in HCV/HIV co-infected Subjects. 16th Conference on Retroviruses and Opportunistic Infections, Montreal, Canada February 2009

  BACKGROUND

• Blackard J, Ma G, Rouster S, Martin C, Shata T, Sherman K. Baseline hepatitis C virus variability does not predict flares in HIV/HCV co-infected persons initiating antiretroviral therapy. 5th International Workshop on HIV and Hepatitis Co-infection, Lisbon, Portugal, June 2009.

  BACKGROUND

• Blackard J, Ma G, Rouster S, Barrett A, Shata T, Sherman K. HIV is frequently detected in liver biopsy tissue. 5th International Workshop on HIV and Hepatitis Co-infection, Lisbon, Portugal, June 2009.

  BACKGROUND

• Shata MT, Bartholomew KA, Rouster SD, Blackard JT, Sterling RK, Bini E, Perelson AS, Goodman ZD and Sherman KE. Strong HCV and HIV immune responses in coinfected subjects who experienced ALT flare and/or rebound HCV viral load after ART initiation. 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, February 2010.

  BACKGROUND

• Blackard JT, Ma G, Martin CM, Rouster SD, Shata MT, Sherman KE. HIV variability in the liver and evidence of possible compartmentalization. AIDS Res Hum Retroviruses. 2011 Oct;27(10):1117-26. doi: 10.1089/aid.2010.0329. Epub 2011 May 4.

  PMID: 21417757 BACKGROUND

• Sherman KE, Guedj J, Shata MT, Blackard JT, Rouster SD, Castro M, Feinberg J, Sterling RK, Goodman Z, Aronow BJ, Perelson AS. Modulation of HCV replication after combination antiretroviral therapy in HCV/HIV co-infected patients. Sci Transl Med. 2014 Jul 23;6(246):246ra98. doi: 10.1126/scitranslmed.3008195.

  PMID: 25101888 RESULT

MeSH Terms

Conditions

Hepatitis C; HIV Infections; Coinfection

Interventions

efavirenz; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Kenneth E. Sherman, MD, PhD

  Unviersity of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 15, 2007
• First Posted: October 17, 2007
• Study Start: April 1, 2006
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: August 12, 2014

Record last verified: 2014-08

Locations

US (2)