Humans ; Mutation/genetics* ; HIV Infections/drug therapy* ; Drug Resistance ; Treatment Failure ; China ; Drug Resistance, Viral/genetics*

Objective: To understand immune escape mutation, drug resistance mutation, and genome evolution information of HBV genome sequence in China. Methods: The whole genome sequence information of HBV in China submitted in GenBank from 1998 to 2021 was selected as the object for analysis. MAFFT method was used for cluster analysis. Analysis of immune escape and drug-resistant mutations was performed using the online tool Gen2pheno. The BEAST 1.10.4 was used for analysis the time evolution of HBV sequences. Results: A total of 5 426 sequences were included in the dataset and distributed in 19 provinces of China. Type C accounted for the highest proportion (59.1%, 3 211/5 426), followed by type B (33.7%, 1 833/5 426). Immune escape mutations were found in 764 sequences (14.1%, 764/5 426). At least one reverse transcriptase region mutation occurred in 98.1% of the sequences. The evolutionary roots of most HBV sequences in China date from around 1801 AD. Conclusion: HBV-resistant mutation rate is high in China. HBV genomes evolve slowly.
China/epidemiology* ; DNA, Viral/genetics* ; Drug Resistance, Viral/genetics* ; Genome, Viral ; Genotype ; Hepatitis B virus/genetics* ; Humans ; Mutation

Drug Resistance, Viral ; genetics ; Hepatitis B virus ; drug effects ; genetics ; Mutation

Drug Resistance, Viral ; genetics ; Hepatitis B virus ; drug effects ; genetics ; Mutation ; Nucleosides ; pharmacology

OBJECTIVETo compare the concordance in predicting genotype HIV-1 drug resistance between In-house method and TRUGENE(TM) or ViroSeq(TM) method.

METHODS25 international proficiency testing (PT) samples received from 2009 to 2013 were detected by three methods, then pairwise comparison results was analyzed to validate their concordance on drug resistance mutation and drug resistance report. To further confirm the results, another 15 serum specimens were detected by In-house and TRUGENE(TM) methods, then compared their results concordance.

RESULTSThe evaluation of the consistency of resistance-associated mutations showed that for 25 PT samples, the consistency was 99.42% (2933/2950) in testing drug resistance mutation sites among the three methods; all pairwise comparison Kappa values >0.81(P < 0.01). The evaluation of the consistency of drug resistance test showed that inconsistent comparison results mainly concentrated in the four nucleoside reverse transcriptase inhibitors zidovudine (AZT), didanosine (ddI), stavudine (d4T), abacavir (ABC), and the inconsistencies were mainly minor. Where the minor inconsistencies between In-house and ViroSeq(TM) methods were 28% (7/25), 28% (7/25), 16% (4/25) and 20% (5/25), respectively. And the inconsistencies between In-house and TRUGENE(TM) method were separately 44% (11/25), 28% (7/25), 36% (9/25) and 28% (7/25);while the inconsistencies between TRUGENE(TM) and ViroSeq(TM) method were separately 24% (6/25), 8% (2/25), 28% (7/25) and 8% (2/25). AZT in the comparison between In-house and ViroSeq(TM) methods, ddI, d4T, ABC and TDF in the comparison between In-house and TRUGENE(TM) methods were moderately consistent (weighted Kappa values were separately 0.54, 0.44, 0.52, 0.42, 0.59, all the P value <0.01). The other compared results were all highly-consistent (weighted Kappa values were 0.61-0.80) or extremely high-consistent (weighted Kappa values were >0.80). For 15 serum specimens, 99.55% (1762/1770) drug resistance mutation sites could be detected by the two methods, the difference about drug results concentrated in AZT, ddI, d4T and ABC.

CONCLUSIONThe In-house genotyping system had a high concordance with commercial TRUGENE(TM) or ViroSeq(TM) genotyping system.

Drug Resistance, Viral ; genetics ; Genes, Viral ; Genotype ; HIV-1 ; drug effects ; genetics ; isolation & purification ; Humans ; Reagent Kits, Diagnostic

Adenine ; analogs & derivatives ; pharmacology ; Drug Resistance, Viral ; genetics ; Genome, Viral ; Hepatitis B virus ; drug effects ; genetics ; Organophosphonates ; pharmacology ; Plasmids ; Viral Proteins ; genetics

Child ; Drug Resistance, Viral ; HIV ; drug effects ; genetics ; HIV Infections ; virology ; Humans

OBJECTIVETo observe the distribution of HBV variants resistant to lamivudine and their relation to clinical manifestations of chronic hepatitis.

METHODSUsing direct sequencing, YMDD (tyrosine-methionine-aspartate-aspartate) variants in patients with chronic HBV were detected before and during treatment with lamivudine. A statistical analysis of the distribution of HBV strains resistant to lamivudine was performed.

RESULTFour variant strains existed in patients before lamivudine treatment, 128 variant resistant strains were noted after 6 mouths of lamivudine treatment including 42 YVDD (valine) variants, 20 YIDD (isoleusine) variants and 66 non-YMDD variants. According to the hepatitis severity, 8 patients were mild, 108 moderate and 12 severe. Viral loading was higher and clinical types were more severe in no-YMDD variants.

CONCLUSIONVariant strains including strains resistant to lamivudine exist naturally before lamivudine treatment, but lamivudine-resistant ones become more dominant after treatment. Liver inflammation is more severe in non-YMDD group.

Antiviral Agents ; pharmacology ; Drug Resistance, Viral ; Genetic Variation ; Hepatitis B virus ; drug effects ; genetics ; Lamivudine ; pharmacology

OBJECTIVETo investigate the evolution of hepatitis B virus (HBV) quasispecies in one patient during lamivudine (LAM) monotherapy and switching to entecavir (ETV) rescue treatment.

METHODSSerum samples were taken at seven different time points during antiviral therapy (0, 24, 48, 60, 72, 96, 152 weeks, respectively), the HBV DNA polymerase gene was amplified, cloned and sequenced to analyze the amino acid substitutions within HBV DNA polymerase gene and distribution of virus quasispecies. Quantitative detection of the HBV wild strains and total virus was performed by amplification refractory mutation system real-time PCR (ARMS-PCR).

RESULTSThree mutation patterns detected during antiviral therapy in the patient: rtM204V, rtM204V+rtL180M and rtM204I. The HBV quasispecies were found always in dynamic variation. The HBV populations were completely replaced with the LAM-resistant variants when the viral breakthrough was encountered during LAM monotherapy. Interestingly, the wild-type variants presented gradually dominant (79.3%) with the decline of HBV DNA load after switching to ETV rescue administration. ARMS-PCR results showed that the wild-type variants account ed for 68.55% of the HBV populations at baseline and this proportion declined to 0.21% when the viral breakthrough emerged under LAM therapy. The wild-type variants gradually increased from week 24 after switching to ETV rescue therapy and the proportion of HBV wild-type variants in the population fluctuated between 16.01% to 26.93%.

CONCLUSIONSThe distribution of virus quasispecies were always in dynamic variation during sequential therapy with nucleotide analogs in chronic hepatitis B patients. Different patterns of dynamic HBV quasispecies may have different contribution in ETV resistance in LMV refractory patients with ETV administration.

Adult ; Antiviral Agents ; therapeutic use ; DNA, Viral ; genetics ; Drug Resistance, Viral ; genetics ; Genotype ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Male ; Mutation

Anti-HIV Agents ; pharmacology ; DNA Mutational Analysis ; methods ; DNA, Viral ; genetics ; Drug Resistance, Viral ; genetics ; Hepatitis B virus ; drug effects ; genetics ; Lamivudine ; pharmacology ; Mutation