Efficacy of PTX+IFN Alpha+ RBV on Hepatitis C Virus Coinfected HIV Patients

Study Overview
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Brief Summary
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Current Hepatitis C virus (HCV) treatment consists of the combination of interferon alpha 2a (IFN-alpha 2a) plus ribavirin (RBV) and it provides sustained virologic responses (SVR) on 54 to 56% on HCV monoinfected patients and this response is even lower on HIV-HCV coinfected patients. A previous study on HCV monoinfected patients showed that the addition of pentoxyfylline (PTX) to a treatment scheme based on interferon-alfa and ribavirin increased SVR on 25%, although it is not known if the same effect is to be obtained in HCV-HIV coinfected patients. On the other hand, other factors such as host genetics, have proved to influence treatment response on HCV infected patients. The best described genetic factor so far is the interleukin 28B (IL28B) polymorphism rs12979860, where a cytosine-cytosine (CC) genotype provides an almost twice increase on SVR than the rest of the genotypes. Therefore, this is a randomized, double blind study to assess the efficacy of pentoxyfylline addition to a treatment scheme based on interferon-alfa and ribavirin in chronic HCV genotype 1, co-infected HIV-1 positive subjects, considering the IL28B polymorphism rs12979860. HIV-HCV coinfected subjects currently receiving Highly active antiretroviral therapy (HAART), with at least 8 months on undetectable HIV viral load and T helper cells count of 200 or higher will be included. Patients will be randomized on one of two groups: Group A: IFN alpha 2a + RBV + PTX Group B: IFN alpha 2a + RBV + placebo Patients will be followed for primary outcome during 72 (for rapid responders) or 96 weeks (for non rapid responses). Outcome measures will be the following: SVR rate 24 weeks after the end of treatment Grade of Hepatic fibrosis from baseline to the end of treatment, measured by transient elastography and the AST to platelet ratio index (APRI index) IL28B rs12979860 genotype The study hypothesis is that the addition of PTX to a treatment scheme based on IFN-alfa2a and RBV in chronic HCV genotype 1, co-infected HIV-1 positive subjects will improve SVR rate and fibrosis progression irrespectively of IL28B rs12979860 genotype.

Official Title
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Efficacy of Pentoxyfylline Addition to a Treatment Scheme Based on Interferon Alpha and Ribavirin on Hepatitis C Virus Coinfected HIV Patients, Considering Interleukin 28B Polymorphism rs12979860

Conditions
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Hepacivirus, HIV Infections

Intervention / Treatment
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* Drug: Pentoxifylline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV/HCV coinfected patients 18 to 65 years old currently receiving HAART non-pregnant women HIV infection controlled as: undetectable viral load (<40 copies/mL) for at least 8 months and T helper cells count of 200 cells/μL or above no contraindications to IFN alpha2a, RBV or PTX treatment sign informed consent form laboratory parameters within acceptable ranges Exclusion Criteria: Women that present a positive pregnancy test during the study Patients that for any reason no longer wish to receive IFN alpha2a, RBV or PTX treatment Serious adverse events that prevent to continue IFN alpha2a, RBV or PTX treatment; such as severe neutropenia, severe thrombocytopenia or severe anemia Presence of an opportunistic infection or malignancy that requires treatment with drugs interacting with IFN alpha2a, RBV or PTX Patients that fail to adhere to treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTX<br>IFN 180 micrograms subcutaneous weekly RBV 400 mg each 12 h, oral PTX 400 mg each 12 h, oral | Drug: Pentoxifylline<br>* Addition of pentoxifylline to current HCV treatment<br>|
| Placebo Comparator: Placebo<br>IFN 180 micrograms subcutaneous weekly RBV 400 mg each 12 h, oral Placebo oral daily | Drug: Placebo<br>* Placebo matching pentoxifylline dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sustained virologic rate 24 weeks post treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection | Primary objective: is to evaluate sustained virologic response at post treatment week 24 following treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection | SVR rate at 24 weeks after the end of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| grade of hepatic fibrosis | The liver stiffness (hepatic fibrosis) will be measured by transient elastography and the APRI index on the baseline visit and then at the follow up visit after treatment, which will be after 72 weeks, for patients that turn out to be quick responders; or 96 weeks, for patients that turn out to be non-quick responders. | Baseline and week 72 (for quick responders) or week 96 (for non-quick responders) | 
| rapid virologic response (RVR) and extended rapid virologic response (eRVR) rates | secondary objective (2): Evaluate rapid virologic response (RVR) and extended rapid virologic response (eRVR) | RVR at week 4 and eRVR at week 48 post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pentoxifylline, Sustained virologic response, Hepatic fibrosis