Ignite Creation Date:
2024-05-06 @ 2:05 AM
Last Modification Date:
2024-10-26 @ 11:13 AM
Study NCT ID:
NCT01964742
Status:
COMPLETED
Last Update Posted:
2015-08-07
First Post:
2013-10-15
Brief Title:
Analysis of Host Genetic Factors in the Occurrence of Anemia and on the Virological Response to a Peg-interferonRibavirin Therapy in HIV-HCV Co-infected Patients
Sponsor:
Assistance Publique Hopitaux De Marseille
Organization:
Assistance Publique Hopitaux De Marseille
Study Overview
Official Title:
Analysis of Host Genetic Factors in the Occurrence of Anemia and on the Virological Response to a Peg-interferonRibavirin Therapy in HIV-HCV Co-infected Patients
Status:
COMPLETED
Status Verified Date:
2015-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 andor 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 SCL29A1A2 and SCL28A2A3 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 SCL29A1A2 and SCL28A2A3 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 SCL29A1A2 and SCL28A2A3 and thus evaluate the overall pharmacogenetic relationships towards RBV-induced anaemia andor virological response to a Peg-IFNRBV therapy
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 SCL29A1A2 and SCL28A2A3 and thus evaluate the overall pharmacogenetic relationships towards RBV-induced anaemia andor virological response to a Peg-IFNRBV therapy
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2013-12 | OTHER | AP HM | None |