Drug Information

Drug (ID: DG00210) and It's Reported Resistant Information

• Name: Entecavir
• Synonyms: Baraclude; ETV; Entecavir hydrate; Entecavir monohydrate; BMS-200475; Baraclude (TN); Entecavir (INN); Entecavir (USAN); Entecavir hydrate (JAN); SQ-34676; 2-amino-1,9-dihydro-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one; 2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-1,9-dihydro-6H-purin-6-one; 2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-1,9-dihydro-6H-purin-6-one-water (1/1); 2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-3H-purin-6-one; 6-H-Purin-6-one-,2-amino-1,9-dihydro-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]; 9-((1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl)guanine monohydrate
• Indication:
  In total 1 Indication(s)
  Hepatitis virus infection [ICD-11: 1E50-1E51]; Approved; [1], [2], [3]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Hepatitis B viral hepatitis [ICD-11: 1E51]; [1], [2], [3]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Hepatitis B viral hepatitis [ICD-11: 1E51]; [4]
• Target: Hepatitis B virus Reverse transcriptase (HBV RT); DPOL_HBVA3; [1]
• Formula: C12H15N5O3
• IsoSMILES: C=C1[C@H](C[C@@H]([C@H]1CO)O)N2C=NC3=C2N=C(NC3=O)N
• InChI: 1S/C12H15N5O3/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20)/t6-,7-,8-/m0/s1
• InChIKey: QDGZDCVAUDNJFG-FXQIFTODSA-N
• PubChem CID: 135398508
• ChEBI ID: CHEBI:473990
• TTD Drug ID: D0KR2J
• VARIDT ID: DR01277
• DrugBank ID: DB00442

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Hepatitis B viral hepatitis [ICD-11: 1E51]

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]

• Molecule Alteration: Missense mutation; p.M204V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.M204I
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.V173L
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.M250V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.V173L
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.M250V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.V173L
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.M250V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.V173L+p.M250V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.I169T+p.V173+p.M250V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.V173L
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.M250V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.V173L+p.M250V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.I169T+p.V173L+p.M250V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.S202I
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.S202G
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.S202I
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.S202G
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G+p.S202I
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204V+p.T184G+p.S202G
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; p.L180M+p.M204I+p.T184G+p.S202I
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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]

• Molecule Alteration: Missense mutation; rtS202I+ rtL180M+ rtM204V
• Resistant Disease: Hepatitis B virus infection [ICD-11: 1E51.0]
• 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