Dual infection was defined as the co-existence of sequences distributed into two or more geno/subtypes. DS results showed the most prevalent genotype in hemophiliac patients was genotype 1b (52.3%), followed by genotype 1a (23.8%) and undetermined (19.0%). All genotype 1a cases were co-infected with HIV. Genotype analyses of NGS consensus sequences yielded consistent results with those of DS, and additionally revealed the genotypes of those undetermined samples to be 1a (4.8%), 2a (9.5%) and 2b (4.8%). Moreover, haplotype reconstruction of HCV hypervariable region (HVR) and NS3 region indicated Selleckchem GSK1120212 that 42.9% of the patients
had dual/triple geno/subtype infections. Focusing on NS3 region, categorical analyses revealed the association between HCV mono-infection and 1b as a dominant genotype (p = 0.008), HIV co-infection and multiple genotypes (p = 0.009), and, histories of blood transfusion (BTF) and multiple genotypes (p = 0.012). Furthermore, the existence of non-1b sequence was tightly associated with HIV co-infection (p = 0.0002), and BTF histories (p = 0.003).
This pilot study demonstrated that multi-geno/subtypic multiple infections may occur more frequently than previously expected, especially in patients having HIV co-infection and BTF histories. Also, our NGS-based haplotype reconstruction approach click here is useful for detecting low-abundant haplotypes undetectable from DS. Whether those harbored viral populations may affect the outcome of DAA therapy should be clarified in forthcoming studies. Disclosures: The following people have nothing to disclose: Masato Ogishi, PFKL Hiroshi Yotsuyanagi, Takeya Tsutsumi, Hiroyuki Gatanaga, Kyoji Moriya, Kazuhiko Koike BACKGROUND MK-5172, a potent HCV NS3/4A protease inhibitor, is being assessed in two phase 2 studies in combination with MK-8742 (a NS5a inhibitor)+/−RBV (C-WORTHy, PN035) and IFN/RBV (PN038) for 12 weeks.
The aim is to characterize the impact of IFN/RBV-free therapy on HRQOL. METHODS HRQOL is assessed using the SF-36v2® Health Survey Acute at baseline, therapy week 4 (TW4), end of therapy (EOT), and follow-up weeks 12 and 24. Means (standard deviations(SD)) are used to describe change from baseline during therapy in the health domain scores and mental component summary (MCS) and physical component summary (PCS) scores. Wilcoxon signed-rank test is used to compare changes from baseline in MCS and PCS scores within each treatment group at TW4 and EOT. RESULTS 123 subjects (24% HIV co-infected, 35% cirrhotic, 27% null-responders to IFN/ RBV) received MK-5172/MK-8742; 125 subjects (23% HIV co-infected, 34% cirrhotic, 26% null-responders to IFN/RBV) received MK-5172/MK-8742/RBV; and 58 mono-infected, treatment-naïve, non-cirrhotic subjects with GT 1 infections received MK-5172 (50 or 100 mg) + IFN/RBV. The SVR rates are high for all treatment groups and subpopulations (86%-100%).