Disease Information

General Information of the Disease (ID: DIS00037)

• Name: Hepatitis B viral hepatitis
• ICD: ICD-11: 1E51

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 6 drug(s) in total

Adefovir

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181T
• Resistant Drug: Adefovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181V
• Resistant Drug: Adefovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.N236T
• Resistant Drug: Adefovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181T+p.N236T
• Resistant Drug: Adefovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181V+p.N236T
• Resistant Drug: Adefovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [4]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; rtN236T+ rtA181V+ rtA181T
• Resistant Drug: Adefovir
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The common LMV substitution for primary resistance involves the amino acid change rtM204V/I arising in the YMDD, a catalytic motif of pol. The compensatory change associated with rtM204V is at rtL180M, rtV173L and rtL80M. ADV resistance is characterized by rtN236T and/or rtA181V/T. ETV resistance tends to emerge in a stepwise manner with the rtS202I change occurring sequentially in viruses already bearing LMV resistance substitution (rtL180M plus rtM204V) mutations, although primary ETV resistance has been reported where these mutations have appeared simultaneously. For LdT, the year 2 resistance rates were 29% in HBeAg-positive and 11% in HBeAg-negative patients with the primary resistance mutation rtM204I. Secondary mutations associated with antiviral therapy, namely rtL80I/V and rtV173L plus rtL180M can also accompany this signature mutation in approximately 2-5% of cases. No definitive TDF-associated mutations have been described in treatment-naive patients taking TDF for up 5 years, but the selection of ADV-therapy associated resistance mutations, rtA181T/V and rtN236T, leads to reduced sensitivity to TDF when the patient is switched, and this has been described in both the clinical and virological setting.

Entecavir

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.M204V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.M204I
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.V173L
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.M250V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.V173L
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.M250V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.V173L
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.M250V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.V173L+p.M250V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.V173+p.M250V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.V173L
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.M250V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.V173L+p.M250V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.V173L+p.M250V
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.S202I
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.S202G
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.S202I
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.S202G
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G+p.S202I
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G+p.S202G
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G+p.S202I
• Resistant Drug: Entecavir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [4]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; rtS202I+ rtL180M+ rtM204V
• Resistant Drug: Entecavir
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The common LMV substitution for primary resistance involves the amino acid change rtM204V/I arising in the YMDD, a catalytic motif of pol. The compensatory change associated with rtM204V is at rtL180M, rtV173L and rtL80M. ADV resistance is characterized by rtN236T and/or rtA181V/T. ETV resistance tends to emerge in a stepwise manner with the rtS202I change occurring sequentially in viruses already bearing LMV resistance substitution (rtL180M plus rtM204V) mutations, although primary ETV resistance has been reported where these mutations have appeared simultaneously. For LdT, the year 2 resistance rates were 29% in HBeAg-positive and 11% in HBeAg-negative patients with the primary resistance mutation rtM204I. Secondary mutations associated with antiviral therapy, namely rtL80I/V and rtV173L plus rtL180M can also accompany this signature mutation in approximately 2-5% of cases. No definitive TDF-associated mutations have been described in treatment-naive patients taking TDF for up 5 years, but the selection of ADV-therapy associated resistance mutations, rtA181T/V and rtN236T, leads to reduced sensitivity to TDF when the patient is switched, and this has been described in both the clinical and virological setting.

Lamivudine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G+p.S202G
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.M204V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.M204I
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181T
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181T+p.N236T
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181V+p.N236T
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.V173L
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.M250V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.V173L
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.M250V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.V173L
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.M250V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.V173L+p.M250V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.V173+p.M250V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.V173L
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.M250V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.V173L+p.M250V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.V173L+p.M250V
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.S202I
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.S202G
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.S202I
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.S202G
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G+p.S202I
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G+p.S202G
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G+p.S202I
• Resistant Drug: Lamivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [5]

• Resistant Disease: Recurrent hepatitis B virus [ICD-11: 1E51.1]
• Molecule Alteration: Mutation; p.L180M+p.M204V+p.M204I
• Resistant Drug: Lamivudine
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Sequencing assay
• Mechanism Description: The most serious problem with lamivudine treatment is the time-dependent emergence of drug resistance by a methionine to valine or isoleucine substitution (rtM204V/I) with or without a leucine to methionine substitution (rtL180M) in the HBV-DNA polymerase gene.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [4]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; rtM204V+ rtM204I+ rtL180M+ rtV173L+ rtL80M
• Resistant Drug: Lamivudine
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The common LMV substitution for primary resistance involves the amino acid change rtM204V/I arising in the YMDD, a catalytic motif of pol. The compensatory change associated with rtM204V is at rtL180M, rtV173L and rtL80M. ADV resistance is characterized by rtN236T and/or rtA181V/T. ETV resistance tends to emerge in a stepwise manner with the rtS202I change occurring sequentially in viruses already bearing LMV resistance substitution (rtL180M plus rtM204V) mutations, although primary ETV resistance has been reported where these mutations have appeared simultaneously. For LdT, the year 2 resistance rates were 29% in HBeAg-positive and 11% in HBeAg-negative patients with the primary resistance mutation rtM204I. Secondary mutations associated with antiviral therapy, namely rtL80I/V and rtV173L plus rtL180M can also accompany this signature mutation in approximately 2-5% of cases. No definitive TDF-associated mutations have been described in treatment-naive patients taking TDF for up 5 years, but the selection of ADV-therapy associated resistance mutations, rtA181T/V and rtN236T, leads to reduced sensitivity to TDF when the patient is switched, and this has been described in both the clinical and virological setting.

Telbivudine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.M204I
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181T
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181T+p.N236T
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181V+p.N236T
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.V173L
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.M250V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.V173L
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.M250V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.V173L
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.M250V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.V173L+p.M250V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.V173+p.M250V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.V173L
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.M250V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.V173L+p.M250V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.V173L+p.M250V
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.S202I
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.S202G
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.S202I
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.S202G
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G+p.S202I
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G+p.S202G
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G+p.S202I
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G+p.S202G
• Resistant Drug: Telbivudine
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [4]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; rtM204I+ rtL80I+ rtL80V+ rtV173L+ rtL180M
• Resistant Drug: Telbivudine
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The common LMV substitution for primary resistance involves the amino acid change rtM204V/I arising in the YMDD, a catalytic motif of pol. The compensatory change associated with rtM204V is at rtL180M, rtV173L and rtL80M. ADV resistance is characterized by rtN236T and/or rtA181V/T. ETV resistance tends to emerge in a stepwise manner with the rtS202I change occurring sequentially in viruses already bearing LMV resistance substitution (rtL180M plus rtM204V) mutations, although primary ETV resistance has been reported where these mutations have appeared simultaneously. For LdT, the year 2 resistance rates were 29% in HBeAg-positive and 11% in HBeAg-negative patients with the primary resistance mutation rtM204I. Secondary mutations associated with antiviral therapy, namely rtL80I/V and rtV173L plus rtL180M can also accompany this signature mutation in approximately 2-5% of cases. No definitive TDF-associated mutations have been described in treatment-naive patients taking TDF for up 5 years, but the selection of ADV-therapy associated resistance mutations, rtA181T/V and rtN236T, leads to reduced sensitivity to TDF when the patient is switched, and this has been described in both the clinical and virological setting.

Tenofovir

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181T
• Resistant Drug: Tenofovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181V
• Resistant Drug: Tenofovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.N236T
• Resistant Drug: Tenofovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181T+p.N236T
• Resistant Drug: Tenofovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [1], [2], [3]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; p.A181V+p.N236T
• Resistant Drug: Tenofovir
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Plasma; Blood; Homo sapiens (Human); N.A.
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: HBV genotyping and sequencing assay
• Experiment for Drug Resistance: Pathological response evaluation assay
• Mechanism Description: The primary resistance mutations in the RT region at sites 169, 180, 181, 184, 202, 204, 236 and 250 have been shown to be involved in cross-resistance to anti-HBV agents via four pathways of viral evolution based on the different structures of the five NAs.

Tenofovir disoproxil fumarate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: HBV Polymerase/reverse transcriptase domain (HBV RT) [4]

• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• Molecule Alteration: Missense mutation; rtA181T+ rtA181V+ rtN236T
• Resistant Drug: Tenofovir disoproxil fumarate
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The common LMV substitution for primary resistance involves the amino acid change rtM204V/I arising in the YMDD, a catalytic motif of pol. The compensatory change associated with rtM204V is at rtL180M, rtV173L and rtL80M. ADV resistance is characterized by rtN236T and/or rtA181V/T. ETV resistance tends to emerge in a stepwise manner with the rtS202I change occurring sequentially in viruses already bearing LMV resistance substitution (rtL180M plus rtM204V) mutations, although primary ETV resistance has been reported where these mutations have appeared simultaneously. For LdT, the year 2 resistance rates were 29% in HBeAg-positive and 11% in HBeAg-negative patients with the primary resistance mutation rtM204I. Secondary mutations associated with antiviral therapy, namely rtL80I/V and rtV173L plus rtL180M can also accompany this signature mutation in approximately 2-5% of cases. No definitive TDF-associated mutations have been described in treatment-naive patients taking TDF for up 5 years, but the selection of ADV-therapy associated resistance mutations, rtA181T/V and rtN236T, leads to reduced sensitivity to TDF when the patient is switched, and this has been described in both the clinical and virological setting.

References

• Ref 1: HBVdb: a knowledge database for Hepatitis B Virus. Nucleic Acids Res. 2013 Jan;41(Database issue):D566-70. doi: 10.1093/nar/gks1022. Epub 2012 Nov 3.
• Ref 2: Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 28.
• Ref 3: Trends in hepatitis B virus resistance to nucleoside/nucleotide analogues in North China from 2009-2016: A retrospective study. Int J Antimicrob Agents. 2018 Aug;52(2):201-209. doi: 10.1016/j.ijantimicag.2018.04.002. Epub 2018 Apr 12.
• Ref 4: Hepatitis B antivirals and resistance .Curr Opin Virol. 2013 Oct;3(5):495-500. doi: 10.1016/j.coviro.2013.08.006. Epub 2013 Sep 7. 10.1016/j.coviro.2013.08.006
• Ref 5: A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis .J Gastroenterol Hepatol. 2008 May;23(5):794-803. doi: 10.1111/j.1440-1746.2007.05240.x. Epub 2007 Dec 14. 10.1111/j.1440-1746.2007.05240.x