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Mixed HCV Genotype Infection and Response to anti-HCV treatment in HIV/HCV Co-Infected Patients

Mixed HCV Genotype Infection and Response to anti-HCV treatment in HIV/HCV Co-Infected Patients. Lucy Porrino, Sabrina Bagaglio, Giulia Morsica, Giulia Gallotta, Hamid Hasson, Laura Galli,Vega Rusconi, Adriano Lazzarin, Caterina Uberti-Foppa

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Mixed HCV Genotype Infection and Response to anti-HCV treatment in HIV/HCV Co-Infected Patients

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  1. Mixed HCV Genotype Infection and Response to anti-HCV treatment in HIV/HCV Co-Infected Patients Lucy Porrino, Sabrina Bagaglio, Giulia Morsica, Giulia Gallotta, Hamid Hasson, Laura Galli,Vega Rusconi, Adriano Lazzarin, Caterina Uberti-Foppa Infectious Diseases Dept, San Raffaele Scientific Institute, Milan, Italy WEAB0102

  2. Background • The frequency of mixed infection in HCV monoinfection is about 2-13% (Schroter et al. 2003; Qian et al. 2000) • There is a single study on viral infections with different genotypes in HIV/HCV coinfected patients and has not been evaluated the performance of the genotype during the anti-viral therapy (Soriano et al. 2005) • Previous reports from Japan identified a mutational pattern within the core protein (70Q-91M) of HCV-1b related to the responsiveness to standard treatment for HCV • This finding possibly mediated by an interaction with interferon signalling cellular protein STAT-1

  3. AIM To determine the HCV genotype pattern and core domain in HIV/HCV coinfected patients during anti-HCV treatment

  4. Sustained Virological Response = (SVR) HCV-RNA negativity at 24-weeks of treatment and maintainment up to 72 weeks No Response (NR) = ≤2 Log decrease of HCV-RNA at 12-weeks Relapse (RE) post-treatment = HCV-RNA positivity during follow up Study Patients • A pilot clinical trial (Kamon2) was conducted to compare LPV/r monotherapy and LPV/r-based HAART during anti-HCV therapy • A virological sub-study was performed on patients HIV/HCV coinfected enrolled in Kamon2 • Patients were analyzed according to response to anti-HCV treatment

  5. Methods • Sequence analysis of HCV-5’ UTR was performed in plasma at different time points: baseline (BL), during 48 weeks treatment and after treatment • The entire sequence of core was inferred in plasma at BL, during treatment and/or after treatment. All these sequences were compared with the respective prototype (based on HCV genotyping)

  6. BaselineCharacteristics of HIV/HCV Coinfected Individuals According to Anti-HCV Treatment Response

  7. HCV Genotype Pattern in NR during Follow-Up • 6 (55%) maintained the same HCV genotype during follow up • 5 (45%) showed an alternance of HCV genotype in plasma lost in follow up lost in follow up lost in follow up

  8. G1-G4 vs G2-G3 G1 vs G3 p= 0.0276 p= 0.018 Core sequence analysis at BL • We obtained the core sequences of 10 SVR and 8 NR • Different distribution of amino acids (aa) mutations in different genotype (G)

  9. Core sequence analysis during follow up in 8 NR patients • 1pt showed the same sequence at each time point • 7 pts showed at least one aa substitution during follow up • This aa mutation were recurrent in specific position

  10. 10 20 30 40 50 ....|....|....|....|....|....|....|....|....|....| MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATR 60 70 80 90 100 ....|....|....|....|....|....|....|....|....|....| KTSERSQPRGRRQPIPKARRPEGRTWAQPGYPWPLYGNEGCGWAGWLLSP 110 120 130 140 ....|....|....|....|....|....|....|....|....| RGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLG *epitope regions **peptide-specific CD4+ T-cell ...in particular • 6/8 showed at least aa substitution in 1-20* and 69-75 **region • 5/8 showed at least aa substitution in 110-115* region

  11. 5/8 pts showed 70Q and/or 91M • 70Q was undetectable at BL in 3pts and appeared during treatment • in 1pt this mutation was detectable at BL and disapperead during treatment • 1pt had 91M at BL and maintained during treatment

  12. NR vs RE p= 0.0056 Characteristic mutational pattern in 2 RE at BL... ...and disappeared during follow up

  13. Conclusions - 5’ UTR analysis • The dynamic pattern of HCV genotypes in half of NR suggests a mixed HCV-infection • The anti-HCV treatment may induce a change balance of dominant strain • Work in progress: ultradeep sequencing (pyrosequencing) will be performed to verify viral population in plasma

  14. Conclusions - Core domain analysis • At BL difficult to treat genotypes are more similar to the respective prototype than “favourable”genotypes • On treatment the most prominent variability of specific residues in specific regions of the core domain could be consequent to the pressure exerted by interferon and/or ribavirin

  15. Thanks to • Infectious Diseases Dept, San Raffaele Scientific Institute, Milan Giulia Morsica Sabrina Bagaglio Marco Merli Alice Dadda Hamid Hasson Giulia Gallotta Laura Galli Vega Rusconi Caterina Uberti-Foppa Adriano Lazzarin • National Institute of Infectious Diseases, Spallanzani, Roma • Infectious Diseases Section, Hospital SS Annunziata, Firenze • Institute of Infectious Diseases, University of Bari, Bari

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