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
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
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.
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