Hepatitis CPhase 1ART and HCVNCT00545558
Effects of Anti-HIV Drugs on the Hepatitis C Virus (HCV) in Adults Infected With Both HCV and HIV
A Phase 1 study testing Efavirenz and Emtricitabine/Tenofovir disoproxil fumarate in people with Hepatitis C and HIV Infections, run by University of Cincinnati at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, HIV Infections
- What is being tested?
- Efavirenz and Emtricitabine/Tenofovir disoproxil fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2006to Mar 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
General Clinical Research Center (GCRC), OH site
Cincinnati, Ohio, 45229
Virginia Commonwealth University, School of Medicine
Richmond, Virginia, 23298
About this study
Official title: Antiretroviral Therapy and the Hepatitis C Virus
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.
Read the detailed description
Coinfection with HCV and HIV occurs in 20% to 30% of HIV infected people in the United States. Individuals with HCV/HIV coinfection tend to have higher HCV viral loads than individuals with HCV alone. However, current evidence suggests that initiation of effective antiretroviral therapy (ART) may be associated with increases in HCV viral load. The purpose of this study is to evaluate changes in HCV viral load associated with the initiation of ART in HCV/HIV coinfected adults.
All participants will receive ART consisting of efavirenz once daily and the co-formulation of emtricitabine and tenofovir disoproxil fumarate (DF) once daily. If participants are unable to tolerate a different regimen would be prescribed.
There will be at least 21 study visits. During the first week of the study, participants will undergo blood draws for viral kinetic sampling and initiation of study medications. Following the first week, there will be weekly visits for 96 weeks. At screening, participants will undergo vital signs measurements, a physical exam, medical history, blood collection, and liver biopsy. During Week 1, participants will be hospitalized for 24 hours for initiation of ART and viral kinetic sampling. Blood draws for viral kinetic sampling of HCV and HIV will be performed at Hours 0, 2, 4, 6, 9, 12, 18, and 24. Participants will return to the clinic or hospital at Hours 48, 72, 96, and 167 for additional viral kinetic sampling. Blood collection will occur at all visits; physical exams, vital signs measurement, a side effects questionnaire, and urine and semen collection will occur at selected visits.
- Conditions
- Hepatitis C, HIV Infections
- Being tested
- Efavirenz, Emtricitabine/Tenofovir disoproxil fumarate
- Keywords
- Antiretroviral Therapy, Highly Active, Coinfection, Treatment Naive
- Medical subject headings
- Hepatitis C, HIV Infections, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EfavirenzDrug
600 mg tablet taken orally daily
Emtricitabine/Tenofovir disoproxil fumarateDrug
200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally daily
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Efavirenz; Drug: Emtricitabine/Tenofovir disoproxil fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Underlying patterns of liver injury and hepatitis C virus (HCV) viral changes after antiretroviral therapy (ART) initiation
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2007 (estimated)
- Study startApr 2006
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kenneth Sherman, University of Cincinnati
- Investigators
- Kenneth E. Sherman, MD, PhD, Principal investigator, Unviersity of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00545558
- Sponsor's protocol ID
- 5R01AI065256-01
- Other IDs
- 5R01AI065256
- Acronym
- ART and HCV
- Status last verified
- Aug 2014
- First submitted
- 15 Oct 2007
- Last updated
- 12 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18380660Shudo 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.
PubMed 18266841Blackard 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.
PubMed 18208497Ma 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
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
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.
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.
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.
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.
PubMed 21417757Sherman 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.
PubMed 25101888
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antiretroviral Therapy and the Hepatitis C Virus
- ClinicalTrials.gov ID
- NCT00545558
- Acronym / sponsor ID
- ART and HCV / 5R01AI065256-01
- Conditions
- Hepatitis C, HIV Infections
- Keywords
- Antiretroviral Therapy, Highly Active, Coinfection, Treatment Naive
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Apr 2006
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 17 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Coinfection with HCV and HIV occurs in 20% to 30% of HIV infected people in the United States. Individuals with HCV/HIV coinfection tend to have higher HCV viral loads than individuals with HCV alone. However, current evidence suggests that initiation of effective antiretroviral therapy (ART) may be associated with increases in HCV viral load. The purpose of this study is to evaluate changes in HCV viral load associated with the initiation of ART in HCV/HIV coinfected adults.
All participants will receive ART consisting of efavirenz once daily and the co-formulation of emtricitabine and tenofovir disoproxil fumarate (DF) once daily. If participants are unable to tolerate a different regimen would be prescribed.
There will be at least 21 study visits. During the first week of the study, participants will undergo blood draws for viral kinetic sampling and initiation of study medications. Following the first week, there will be weekly visits for 96 weeks. At screening, participants will undergo vital signs measurements, a physical exam, medical history, blood collection, and liver biopsy. During Week 1, participants will be hospitalized for 24 hours for initiation of ART and viral kinetic sampling. Blood draws for viral kinetic sampling of HCV and HIV will be performed at Hours 0, 2, 4, 6, 9, 12, 18, and 24. Participants will return to the clinic or hospital at Hours 48, 72, 96, and 167 for additional viral kinetic sampling. Blood collection will occur at all visits; physical exams, vital signs measurement, a side effects questionnaire, and urine and semen collection will occur at selected visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Efavirenz, Drug: Emtricitabine/Tenofovir disoproxil fumarateParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Efavirenz600 mg tablet taken orally daily | Drug | 1 |
| Emtricitabine/Tenofovir disoproxil fumarate200 mg emtricitabine/ 300 mg tenofovir disoproxil fumarate tablet taken orally daily | Drug | 1 |
Primary outcome
Underlying patterns of liver injury and hepatitis C virus (HCV) viral changes after antiretroviral therapy (ART) initiation
Time frame: Throughout study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2014.
- Background: PubMed 18380660Shudo 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.
- Background: PubMed 18266841Shudo 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.
- Background: PubMed 18208497Blackard 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.
- BackgroundMa 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
- BackgroundSherman 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
- BackgroundBlackard 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.
- BackgroundBlackard 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.
- BackgroundShata 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: PubMed 21417757Blackard 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.
- Results publication: PubMed 25101888Sherman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth E. Sherman, MD, PhD principal investigator
Unviersity of Cincinnati
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Efavirenz and Emtricitabine/Tenofovir disoproxil fumarate in people with Hepatitis C and HIV Infections, run by University of Cincinnati at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Underlying patterns of liver injury and hepatitis C virus (HCV) viral changes after antiretroviral therapy (ART) initiation (time frame: Throughout study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00545558, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2014.