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    • Vicenti et al assessed the prevalence of HCV NS A

    2021-12-30

    Vicenti et al. [38] assessed the prevalence of HCV NS3/4A PI resistance mutations in HCV genotype 1-infected PI-naïve individuals, including 66 subjects coinfected with HCV/HIV. They found that 19.3% of isolates have at least one mutation related to PI resistance, and the HCV PI resistance mutations are not significantly associated with HIV coinfection. Similarly, a study by Lisboa-Neto et al. [39] assessed the prevalence of naturally occurring HCV PI mutations in HCV monoinfected and HIV/HCV-coinfected patients in Brazil, which are 22.96 and 20.53%, respectively. The difference in observed mutation rates between HCV monoinfected and HIV/HCV coinfected patients at positions associated with HCV PI resistance was not detected. Another study reported that 16.22% (6/37) sequences obtained from individuals coinfected with HIV/HCV present natural amino NS 11394 polymorphism at positions associated with anti-HCV PI resistance [40]. In contrast, a higher prevalence of HCV PI resistance mutations was found in patients with HIV infection compared with HCV monoinfected patients. In the light of these observations, further studies on larger cohort are needed to confirm whether or not the prevalence of resistant strains in individuals coinfected with HIV/HCV are more prone to HCV protease polymorphisms with respect to HCV monoinfection. In this study, 25.00% (17/68) of the samples had detectable levels of a mutation at position A156. The A156G substitution, known to confer possible resistance to BOC and associated with resistance to vaniprevir (×16 in vitro) and simeprevir (×19 in vitro), was the highest represented mutation, accounting for 23.53% of all the tested samples. One patient contained the substitution A156V, which is a major mutation associated with TVR and BOC resistance [41]. A156G was detected more frequently than A156V, suggesting that the A156G mutation might fit better than the A156V mutation in Chinese patients coinfected with HIV/HCV genotype 1b. Notably, variant A156G was detected in three patients with combination mutations. It remained unclear why the A156G variant was dominant in these patients, and the possible explanation could be that A156G substitution was in conjunction with other substitutions. Different frequencies of substitutions associated with resistance to PIs, such as F43S, T54S, Q80K/R, R155K and D168A/E/G, were also found. In our country, 1.47% of patients with genotype 1b had the Q80K resistance mutation, which has been associated with a reduced treatment response to simiprevir with pegylated interferon (P) and ribavirin (R). In the European region, the overall prevalence of Q80K in genotype 1 is 7.5%, ranging from 0 to 18.2% [42]. Of note, Q80K prevalence is only 0.5% in European genotype 1b patients, and researchers also found that countries with a low Q80K prevalence are driven by the high percentage of genotype 1b patients. These data showed that the ratio of genotype 1a to genotype 1b and HCV geographic distribution may determine Q80K prevalence. Baseline testing for Q80K is recommended in patients with HCV genotype 1a before initiating simeprevir plus PR treatment [43]. However, our data suggested that Q80K baseline testing was not cost-effective in Chinese patients coinfected with HIV/HCV. On the other hand, Zeuzem et al. [44] showed that mutations of R155K or D168V alone or combined with Q80K/R, R155K or D168E in the HCV NS3 region are observed in almost all simeprevir-treated patients with viral breakthrough or relapse, and these emerging mutations reduced susceptibility to simeprevir. As observed in other studies, we also found that mutations of R155K or D168A/E/G were mostly combined with Q80K/R, R155K or A156G. In addition, other amino acid variations, which are not considered as the resistance mutations in HCV NS3/4A region, were also found when comparing with Con1 reference strain. This work confirmed the heterogeneity of NS3 protease sequences in patients coinfected with HIV/HCV. Bartolini et al. [45] noticed the heterogeneity of HCV NS3 is lower in HIV-coinfected patients compared with HCV monoinfected patients. However, data on the natural prevalence of mutations conferring resistance to HCV PIs in patients coinfected with HIV/HCV are limited. Whether there was difference in the natural prevalence of strains resistant to HCV PIs between HCV monoinfected and HIV/HCV-coinfected patients was not well understood. Understanding the frequency of a resistant variant or resistance polymorphisms in the HCV/HIV coinfected, treatment-naïve patients is critical to address their potential impacts on the treatment outcomes. Further analysis is required to evaluate the impact of these mutations on clinical practice.