Analysis of Host Genetic Factors in the Occurrence of Anemia and on the Virological Response to a Peg-interferon/Ribavirin Therapy in HIV-HCV Co-infected Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Assistance Publique Hopitaux De Marseille
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier:
NCT01964742
First received: October 15, 2013
Last updated: November 28, 2013
Last verified: November 2013
  Purpose

The treatment of HCV (hepatitis C virus) infection has made significant progress over the past decade with the therapy combining pegylated interferon (Peg-IFN) to ribavirin (RBV). The cure of HCV infection which consists to obtain a sustained virological response (SVR) (undetectable HCV RNA 24 weeks after end of treatment) is reached in more than 50% of patients infected with HCV. However, this rate is much lower, around 30 to 40% in HIV-HCV co-infected patients and sometimes can be less than 20% for patients infected with HCV genotype 1. Haemolytic anemia is a dose-limiting adverse effect which occurs frequently under RBV therapy. RBV-induced anemia represents the main cause of treatment discontinuation or dose reduction of RBV, thus limiting the chances of achieving a SVR. RBV has a large inter-individual pharmacokinetic variability and a relationship between the occurrence of anemia and RBV concentration was clearly demonstrated. However, other factors, including genetic factors, could be predictive of hematotoxicity and/or a better efficiency. In particular, IL-28B polymorphism analysis, in patients infected with HCV genotype 1, before starting antiviral therapy could predict the response to treatment (positive predictive value). The genetic polymorphism of inosine triphosphate pyrophosphatase (ITPA) is also strongly associated to a protective effect towards the RBV-induced-anemia. But most of these data are issued from studies performed in a Japanese HCV mono-infected population treated with Peg-IFN-RBV therapy for which there is no other causal variant that the rs1127354. Only few studies are reported in the literature in caucasian HIV-HCV co-infected patients. Moreover, data on RBV plasma exposure are very scarce in all these studies showing an impact of the ITPA polymorphism on the occurrence of anemia. In addition, others polymorphisms of SCL29A1/A2 and SCL28A2/A3 coding for RBV transporters, ENT (equilibrative nucleoside transporter) et CNT (concentrative nucleoside transporter) would be associated to either rapid virological response or anemia in HCV infected patients treated by Peg-IFN plus RBV. No study considering both polymorphisms of ITPA, IL-28B, SCL29A1/A2 and SCL28A2/A3 genes and RBV plasma exposure data has so far been conducted in HIV-HCV co-infected patients.

Thus, it would be interesting in a first time to assess the impact of the ITPA polymorphism on both the RBV plasma exposure and the protective effect towards RBV-induced anemia in HIV-HCV co-infected patients. This study could be helpful to the literature for possible further RBV dose adjustments according to ITPA activity.

Then, it would be relevant to further complete these data by assessing other genetic polymorphisms as IL-28B, SCL29A1/A2 and SCL28A2/A3 and thus evaluate the overall pharmacogenetic relationships towards RBV-induced anaemia and/or virological response to a Peg-IFN/RBV therapy.


Condition Intervention
HIV-HCV Co-infected Patients
Genetic: blood samples

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Analysis of Host Genetic Factors in the Occurrence of Anemia and on the Virological Response to a Peg-interferon/Ribavirin Therapy in HIV-HCV Co-infected Patients

Resource links provided by NLM:


Further study details as provided by Assistance Publique Hopitaux De Marseille:

Primary Outcome Measures:
  • blood samples [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: October 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HIV-HCV co-infected patients Genetic: blood samples

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult ≥ 18 years
  • Patients co-infected HIV-HCV (HCV serology and HCV positive CV before starting HCV treatment)
  • Patients who have been treated with combination therapy Peg-IFN/RBV for at least 12 weeks and having at least a given plasma RBV available in the patient record
  • Free Consent, informed and signed

Exclusion Criteria:

  • Adult <18
  • Mono-infection with HCV or HIV
  • Co-infection with HBV (HBsAg +)
  • Pregnant or lactating woman
  • Not obtaining free and informed consent signed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01964742

Contacts
Contact: olivia zaegel faucher olivia.zaegel@ap-hm.fr

Locations
France
Assistance Publique Hopitaux de Marseille Recruiting
Marseille, France, 13354
Contact: olivia zaaegel faucher       olivia.zaegel@ap-hm.fr   
Principal Investigator: olivia zaegel         
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Investigators
Study Director: LOIC MONDOLONI Assistance Publique Hopitaux De Marseille
  More Information

No publications provided

Responsible Party: Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier: NCT01964742     History of Changes
Other Study ID Numbers: 2013-A00505-40, 2013-12
Study First Received: October 15, 2013
Last Updated: November 28, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
Interferons
Ribavirin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014