Dataset Information

High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico.

ABSTRACT:

Background and aims

Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations.

Methods

This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger's sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool.

Results

Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L (n=2) and rt180M+rt204V+rt202G (n=1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18).

Conclusions

The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico.

SUBMITTER: Jose-Abrego A

PROVIDER: S-EPMC10412697 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico.

Jose-Abrego Alexis A Roman Sonia S Rebello Pinho João Renato JR Gomes-Gouvêa Michele Soares MS Panduro Arturo A

Journal of clinical and translational hepatology 20230607 5

<h4>Background and aims</h4>Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations.<h4>Methods</h4>This cross-sectional study a ...[more]

PMID: 37577226

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Project description:Antiviral resistance is now the single most important factor in treatment failure using nucleos(t)ide analogues (NA). Primary drug resistance mutations refer to amino acid change(s) that result in reduced susceptibility to an antiviral agent. Secondary compensatory mutations restore replication defects associated with primary drug resistance and may be associated with low level reduced susceptibility. Several evolutionary pathways of drug resistant HBV have been observed in patients treated with NAs. It is possible that the drug resistance mutations selected with one agent may affect the efficacy of other NAs. Several major HBV-evolutionary NA-resistance pathways (rtM204I/V, rtN236T and rtA181T/V) have now been characterised. The rtM204V/I pathway is responsible for resistance to the L: -nucleosides, such as lamivudine (LMV), telbivudine (LdT) and clevudine (CLD), and also entecavir (ETV), whilst the rtN236T pathway is responsible for adefovir (ADV) and tenofovir (TFV) resistance. Both pathways are associated with clusters of secondary mutations that can affect subsequent treatment with NAs (rtT184G, rtS202I) such as ETV. The third pathway, rtA181T/V, is associated with resistance to LMV and ADV and is a potential multi-drug resistance pathway and will probably have an impact on TFV sensitivity, either alone or with the rtN236T. In naïve patients treated with ETV, atleast three mutations arising at the same time are required: rtL180M + rtM204V plus either one of rtT184, rtS202 or rtM250 codon changes. Finally, in highly drug-experienced patients, clusters of mutations such as rtA181T/I233V/N236T/M250L, all on the one dominant HBV genome, are being detected which are associated with multi-drug resistance. Sequential treatment with nucleos(t)ide analogue reverse transcriptase inhibitors (NRTI) promotes multidrug resistance. It is likely, therefore, that development of multi-drug resistance could be reduced by combination therapy optimised to individual viral phenotypes.

Project description:Hepatitis B virus (HBV) infection remains a major public health threat in the Middle East and North Africa (MENA). Phylogenetic analysis of HBV can be helpful to study the putative transmission links and patterns of inter-country spread of the virus. The objectives of the current study were to analyze the HBV genotype/sub-genotype (SGT) distribution, reverse transcriptase (RT), and surface (S) gene mutations and to investigate the domestic transmission of HBV in the MENA. All HBV molecular sequences collected in the MENA were retrieved from GenBank as of 30 April 2021. Determination of genotypes/SGT, RT, and S mutations were based on the Geno2pheno (hbv) 2.0 online tool. For the most prevalent HBV SGTs, maximum likelihood phylogenetic analysis was conducted to identify the putative phylogenetic clusters, with approximate Shimodaira-Hasegawa-like likelihood ratio test values ≥ 0.90, and genetic distance cut-off values ≤ 0.025 substitutions/site as implemented in Cluster Picker. The total number of HBV sequences used for genotype/SGT determination was 4352 that represented a total of 20 MENA countries, with a majority from Iran (n = 2103, 48.3%), Saudi Arabia (n = 503, 11.6%), Tunisia (n = 395, 9.1%), and Turkey (n = 267, 6.1%). Genotype D dominated infections in the MENA (86.6%), followed by genotype A (4.1%), with SGT D1 as the most common in 14 MENA countries and SGT D7 dominance in the Maghreb. The highest prevalence of antiviral drug resistance was observed against lamivudine (4.5%) and telbivudine (4.3%). The proportion of domestic phylogenetic clustering was the highest for SGT D7 (61.9%), followed by SGT D2 (28.2%) and genotype E (25.7%). The largest fraction of domestic clusters with evidence of inter-country spread within the MENA was seen in SGT D7 (81.3%). Small networks (containing 3-14 sequences) dominated among domestic phylogenetic clusters. Specific patterns of HBV genetic diversity were seen in the MENA with SGT D1 dominance in the Levant, Iran, and Turkey; SGT D7 dominance in the Maghreb; and extensive diversity in Saudi Arabia and Egypt. A low prevalence of lamivudine, telbivudine, and entecavir drug resistance was observed in the region, with almost an absence of resistance to tenofovir and adefovir. Variable proportions of phylogenetic clustering indicated prominent domestic transmission of SGT D7 (particularly in the Maghreb) and relatively high levels of virus mobility in SGT D1.

Dataset Information

High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico.

Background and aims

Methods

Results

Conclusions

Publications

High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico.

Similar Datasets

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