This hypothesis is strengthened by the fact that the two selected substitutions, sS143T and sM197T, are located at the external side of HBsAg, within known immunodominant epitopes. However, this was noted in only 1 patient in this study. Adefovir dipivoxil is still widely used worldwide, alone or in combination with lamivudine. As shown in this study, variants with amino acid substitutions histone deacetylase activity known to confer resistance to various nucleoside/nucleotide analogs, including adefovir, can be detected in a substantial proportion of treatment-naïve patients with CHB. Larger scale studies are now required to determine
whether baseline testing with UDPS will be useful to orientate HBV treatment strategies. BAY 73-4506 datasheet In addition, next-generation sequencing methods, such as UDPS, could be of considerable interest for early diagnosis of viral resistance during antiviral therapy. Indeed, with our approach, resistance could be diagnosed at approximately the same time as with cloning and sequencing (thus considerably earlier than with population sequencing), in a user-friendly and rapid way, compatible
with clinical practice (data not shown). This will be facilitated in the future when the costs are reduced and the technology becomes easily available through specialized platforms. In conclusion, using an original software package for analyzing viral sequences generated by UDPS and other next-generation sequencing methods in the context of antiviral resistance, (1) we showed that substitutions conferring HBV
resistance to nucleoside/nucleotide analogs preexist in patients who have never been exposed to these drugs, (2) we characterized the complex and heterogeneous dynamics of adefovir-resistant viral populations in a group of HBV-infected patients in whom resistance emerged during long-term adefovir therapy, and (3) we identified thus far unknown amino acid substitutions that appeared to play an important role in HBV resistance to adefovir. These findings will also be helpful for understanding resistance to tenofovir, which shows cross-resistance click here with adefovir in vitro. Our findings imply that next-generation sequencing data analysis will have a number of applications in viral resistance assessment, as we recently reported with hepatitis C virus and human immunodeficiency virus.[29, 30] The authors thank Thierry Ravard for his help with mathematical modeling and Françoise Roudot-Thoraval for her help with statistical tests, as well as Katyna Borroto-Esoda and Manh-Tong Dao. Additional Supporting Information may be found in the online version of this article. “
“Invasive fungal infection (IFI) related to surgery in elderly patients is often associated with high morbidity and mortality.