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

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

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.

Study Overview

• Status: Unknown
• Conditions: HIV Infections; Hepacivirus
• Intervention / Treatment: Drug: Pentoxifylline; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil de Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with CC genotype on the IL28B rs12979860 polymorphism	We will compare the percentage of patients with CC genotype among patients that achieved sustained virologic response and those who did not achieved it. This is to confirm if the intervention provides a beneficial effect, irrespectively of host genetic factors.	week 72

Collaborators and Investigators

• Sponsor: Centro Universitario de Ciencias de la Salud, Mexico

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): March 1, 2015
• Study Completion (Anticipated): March 1, 2016

Study Registration Dates

• First Submitted: December 3, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (Estimate): December 11, 2013

Study Record Updates

• Last Update Posted (Estimate): December 11, 2013
• Last Update Submitted That Met QC Criteria: December 6, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Hepatic fibrosis; Pentoxifylline; Sustained virologic response
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: PTX-HCV/HIV