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HIV InfectionsPhase 2NCT00031343

The Impact of HAART on Response to Hepatitis C Treatment in Patients Taking Peginterferon Alpha-2b and Ribavirin

A Phase 2 study testing highly active antiretroviral therapy (HAART) in people with HIV Infections and Hepatitis C, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will evaluate how controlling HIV infection with HAART (highly active antiretroviral therapy) affects the response to hepatitis C treatment with peginterferon alpha-2b and ribavirin in HIV-infected patients with chronic hepatitis C. HIV worsens liver disease caused by hepatitis C. Read more about this study

Who is it for?
Any age
Conditions the study is for
HIV Infections, Hepatitis C
What is being tested?
highly active antiretroviral therapy (HAART)
How many people
128 participants
Where
1 siteUnited States
Study dates
Feb 2002to Apr 2004
Phase
Phase 2
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age greater than or equal to 18 years
  • Documentation of HIV-1 infection by a licensed ELISA test and confirmed by a Western Blot
  • CD4 greater than or equal to 500 cells/mm(3) or CD4 greater than or equal to 350 cells/mm(3) and HIV VL less than or equal to 40,000 copies per milliliter
  • CD4 nadir not below 200 cells/mm(3)
  • If not HAART naive, history of HIV VL suppression while on HAART treatment.
  • Patients who are currently on HAART but do not meet criteria for the initiation of HAART according to current DHHS guidelines must be willing to come off their regimen 3 months prior to study initiation.
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  • Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C antibody.
  • HCV RNA level greater than 2000 copies per milliliter by polymerase chain reaction
  • Patients naive to HCV treatment at time of enrollment.
  • Serum creatinine less than or equal to 1.5 mg/dL
  • Serum phosphorus greater than or equal to 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL)
  • Neutrophil count greater than or equal to 1000 cells/mm(3)
  • Platelets greater than or equal to 75,000/mm(3)
  • Hemoglobin greater than or equal to 8.0 mg/dL
  • ALT less than 7 X the NIH upper limit of normal
  • Not pregnant or breast-feeding. Pregnancy tests must be negative within two weeks prior to dosing with study medications.
  • Due to the teratogenic effects of ribavirin, for women of child-bearing age, the use of effective contraception during the study will be required. These include abstinence, surgical sterilization of either partner, barrier methods such as a diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter the metabolism of hormonal contraception.
  • Patients must have a primary MD responsible for their HIV infection and liver disease.
  • Willing to designate a person for durable power of attorney on NIH form for medical research and medical care purposes at the NIH Clinical Center.
  • Ability to learn how to safely inject medication subcutaneously or have a family member, relative or partner who is willing to learn to inject study medication.
  • Competency to sign informed consent and willingness to comply with study requirements and clinic policies.
  • Willingness to have blood and tissue specimens stored in NIH facilities.
  • Child-Pugh score less than 6.
  • Willingness for female patients to practice at least two reliable forms of effective contraception during treatment with ribavirin. Effective means of contraception include barrier and hormonal methods.
  • Willingness for male patients to practice effective contraception during treatment with ribavirin, including barrier methods.

Who cannot join

  • PT-INR (in the absence of anti-cardiolipin Ab) by greater than or equal to 2.
  • Organ transplant recipient
  • Recent HIV seroconverters (must be 6 months or more with documented HIV diagnosis).
  • Patients who are medically indicated to begin HAART therapy
  • Elevated alpha-fetoprotein level (greater than or equal to 100 ng/mL).
  • Coexisting neoplastic disease requiring cytotoxic therapy.
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  • Have had cancer other than Kaposi's sarcoma of the skin, other skin cancers treated by resection, Bowen's disease, or localized cervical or anal cancer in the 5 years prior to enrollment
  • Have had significant renal dysfunction within the previous 12 months or evidence of significant protein wasting
  • Severe cardiac or pulmonary decompensation as assessed by the PI.
  • Severe liver decompensation or advanced cirrhosis patients
  • Severe psychiatric disorder that would interfere with the adherence to protocol requirements.
  • Autoimmune disorders including inflammatory bowel diseases, and optic neuritis as assessed by the PI.
  • Uncontrolled seizure disorder
  • Severe retinopathy.
  • Direct bilirubin more than or equal to 2 times ULN.
  • No patients using long-term systemic corticosteroids, immunosuppressives, IL-2, or cytotoxic agents within 60 days of enrollment.
  • Active systemic infections (other than hepatitis C and HIV).
  • Liver disease caused by reasons other than hepatitis C like HBV, HDV, Wilson's hemochromatosis, or autoimmune hepatitis (ANA greater than or equal to 3.0) except history of drug-associated hepatitis with discontinuation of the causative agent.
  • Hepatic mass suggestive of hepatocellular carcinoma.
  • Current alcohol or substance use.
  • Any systemic illness that will make it unlikely that the subject will be able to return to NIH for the required study visits.
  • Evidence of gastrointestinal malabsorption, chronic nausea, or vomiting
  • Any pre-existing hemoglobinopathy.
  • Patients taking any of the following medications: rifampin/rifampicin, rifabutin, pyrazinamide, isoniazid, ganciclovir, thalidomide, oxymetholone, immunomodulatory treatments (including supraphysiologic doses of steroids and radiation, and antineoplastic agents).
  • Patients taking any investigational drugs and herbal remedies, and other complementary/alternative medications for possible or perceived effects against HCV.
  • Patients cannot be receiving IL-2 during participation in this study.
  • Ribavirin is contraindicated in male partners of women who are pregnant. Therefore, potential male patients with pregnant female partners will be excluded.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institute of Allergy and Infectious Diseases (NIAID)

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Randomized, Controlled Study to Assess the Impact of Highly Active Antiretroviral Therapy to Hepatitis C Therapy in Patients Coinfected With HIV-1 and Treated With Peginterferon Alpha-2b and Ribavirin

This study will evaluate how controlling HIV infection with HAART (highly active antiretroviral therapy) affects the response to hepatitis C treatment with peginterferon alpha-2b and ribavirin in HIV-infected patients with chronic hepatitis C. HIV worsens liver disease caused by hepatitis C. Since treatment of HIV infection with HAART improves immune function, it may be beneficial to start HAART before treating HCV.

HIV-infected patients 18 years of age and older with chronic hepatitis C infection may be eligible for this study. Patients must have an HCV viral load greater than 2000 copies/mL and a CD4 count that is either more than 500 cells/mm3, or more than 350 cells/mm3 with an HIV viral load no greater than 40,000 particles/mL. Candidates will be screened for current or previous diseases, conditions or treatments that may exclude them from this study. Screening includes a medical history and physical examination, eye examination, blood and urine tests, chest X-ray, electrocardiogram (EKG), liver ultrasound, and, possibly, a liver biopsy, if a recent one is not available. The liver biopsy is optional and is done to determine the severity of liver disease. Patients will be sedated for this test. 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. Patients remain in the hospital overnight for monitoring. Women of childbearing age will have a pregnancy test.

Read more

Patients enrolled in the study will be randomly assigned to one of the following treatment groups: 1) pegylated interferon and ribavirin for 48 weeks (control group); or 2) HAART for 6 months, followed by 48 weeks of pegylated interferon and ribavirin.

HAART group - Patients taking HAART will be followed in the clinic every 2 weeks for the first month and then monthly for the next 5 months. After 6 months of HAART they will begin taking pegylated interferon and ribavirin and will follow the dosing and follow-up schedule outlined below for patients in the control group.

Control group - Patients will have weekly injections under the skin of peginterferon alpha-2b and ribavirin pills daily by mouth. Clinic visits will be scheduled as follows:

  • Days 1, 3, 7, and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV. HCV medications will be injected on days 7 and 21.
  • 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 pegylated interferon and ribavirin treatment and its effect on the HCV infection. Eye examinations will be done every 3 months.
  • Week 48 or end of treatment - Treatment with pegylated interferon and ribavirin will stop after 48 weeks. At this time (or earlier for those who do not complete the 48 weeks of treatment), patients will return to the clinic for a routine visit, blood tests (including a test for hepatitis B) and abdominal ultrasound. Patients may also be hospitalized for 2 days for a repeat optional liver biopsy.
  • Week 72 and extended follow-up visits - At week 72, patients will return for blood tests and a routine clinic visit. HCV viral load will be measured. Follow-up visits every 3 months for an additional year will include a blood test to measure HCV viral load and a complete physical examination.
Read the detailed description

Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) has risen dramatically since the explosion of the HIV pandemic twenty years ago, with one third of all HIV positive persons also infected with HCV. Numerous studies have suggested that HIV exacerbates several steps in the natural history of hepatitis C, and as survival among HIV-infected patients increases, hepatitis C-related morbidity and mortality is expected to follow a similar trend in coinfected patients. Some investigators advocate the initiation of highly active antiretroviral therapy (HAART) for this population prior to the initiation of HCV therapy. It is postulated that HAART will improve the host immune function by increasing the CD4+ cell count and decreasing HIV viral load, thought to be advantageous for patients starting HCV therapy. Despite its promising hypothesis, whether HAART ultimately leads to a reduction in HCV load in coinfected persons remains controversial. This is a non-blinded, randomized controlled trial to evaluate the impact of HAART on the immunologic, virologic, and clinical responses to HCV treatment with peginterferon and ribavirin in coinfected individuals with CD4 greater than or equal to 500 cells/mm (3) or greater than or equal to 350 cells/mm(3) and a viral load less than or equal to 40,000 copies/mL. The study will also address the safety and efficacy of administering a combination of HAART along with peginterferon alpha-2b and ribavirin to HIV-infected individuals. 128 patients who are coinfected with HIV and HCV will be recruited for the study and randomized to receive one of two treatment regimens: 1) control group: will be treated with peginterferon alpha-2b and ribavirin for 48 weeks, or 2) experimental group: will be treated with highly active antiretroviral therapy for six months. At that point, they will begin receiving peginterferon alpha-2b and ribavirin at the same doses as the control group for 48 weeks. During the 72-week follow up period, these patients will be monitored for both HCV and HIV viral loads and CD4+ lymphocyte counts. The results of the study will enable us to better delineate the relationship between the immune reconstitution effects induced by HAART and the clinical, immunologic, and virologic responses of coinfected persons treated with peginterferon and ribavirin. In addition, evaluating the safety of coadministering peginterferon, ribavirin, and HAART will further refine the best therapeutic regimen for this patient population.

Being tested
highly active antiretroviral therapy (HAART)
Keywords
Liver Disease, Virologic Response, Immune Mechanisms, Eradication, Antiviral Therapy, HIV, Hepatitis C, HCV, Coinfection
Medical subject headings
HIV Infections, Hepatitis C, Liver Diseases, Coinfection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • highly active antiretroviral therapy (HAART)Drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2002 (estimated)
  2. Study startFeb 2002
  3. Study completionApr 2004

Resources

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 2
Primary purpose
Treatment
Enrolment
128 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00031343
Sponsor's protocol ID
020139
Other IDs
02-I-0139
Status last verified
Apr 2004
First submitted
2 Mar 2002
Last updated
4 Mar 2008
Results posted
No

Publications

  • National Institutes of Health Consensus Development Conference Panel statement: management of hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):2S-10S. doi: 10.1002/hep.510260701.

    PubMed 9305656

  • Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am. 1994 Sep;23(3):437-55.

    PubMed 7989088

  • Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, Hu PY, Miller JK, Gerber MA, Sampliner RE, et al. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med. 1992 Dec 31;327(27):1899-905. doi: 10.1056/NEJM199212313272702.

    PubMed 1280771

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing highly active antiretroviral therapy (HAART) in people with HIV Infections and Hepatitis C, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 25 inclusion and 27 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 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00031343, which also lists 3 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 4 Mar 2008.

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