Next, the frequency of polymerase drug resistance mutations was assessed in the study samples. The sequences of the polymerase gene derived from the patient samples Crenolanib mechanism were analyzed using the DRI, G2P, and STAN interpretation systems. The data revealed that in 22 of the 237 sequences (9%) polymerase mutations which are associated with drug resistance were present. The concordance of mutations identified as relevant for resistance between all interpretation tools was 100%. However, the interpretation of these mutations by the three algorithms differs. Where STAN just lists detected drug resistance-associated mutations, G2P and DRI rate them on a scale of three resistance ��levels�� (susceptible, possibly resistant, and resistant), and some mutations are assigned a different rating by the respective system.
When rating the mutations, G2P and DRI concurred in 9 of 22 cases. A detailed overview of the concordant and discordant results obtained by the two assays is presented in Table 1. Table 1 Sequence analysis results for resistance-associated mutations in the polymerase sequence (P) of samples and their rating as determined by DRI and G2P We further investigated whether and to what extent drug resistance mutations in P occur in the patient samples which potentially influence antibody binding and/or HBsAg secretion in the corresponding S sequence. Since neither of the interpretation algorithms includes these mutations, they were assessed according to previously published data (23).
The analysis of the 22 sequences with resistance mutations in P revealed that 19 of these sequences contained mutations which potentially influence antibody binding and/or HBsAg secretion in the corresponding S sequence, namely, pA181T, pM204I, and pM204V. Adding these sequences to those with MARABs as detected by the algorithms brings the total of sequences with mutations possibly influencing quantitative detection of HBsAg (MUPIQHs) to 72 (30% of all sequences analyzed) when using DRI and to 44 (19% of all sequences analyzed) when using G2P. An overview of the mutations in P detected in our sequences is shown in Table 1. Genotyping and assignment of sequences to patients’ country of origin. We then analyzed the HBV sequences for their genotype. Alignment and phylogenetic analysis using the respective P nucleotide sequence was performed, and the samples were analyzed by three interpretation systems.
The concordance of predicted genotypes between the three interpretation systems used was 100%. Overall, 37 samples were assigned to genotype A, 17 to genotype B, 23 to genotype C, 155 to genotype D, and 5 to genotype E. The patients’ country of origin could be determined by chart review in 186 cases. The association between country group of origin and genotype is presented in Fig. 2. Fig AV-951 2 HBV genotypes of the 237 individuals included in the study, grouped according to the patients’ region of origin.