Characterization of drug-resistance mutations in HBV D-genotype chronically infected patients, naïve to antiviral drugs

R. Salpini, V. Svicher, V. Cento, C. Gori, A. Bertoli, F. Scopelliti, V. Micheli, T. Cappiello, A. Spanò, G. Rizzardini, G. M. De Sanctis, C. Sarrecchia, M. Angelico, C. F. Perno

Research output: Contribution to journalArticle

Abstract

Presence of drug-resistance mutations in drug-naïve hepatitis B virus (HBV) infected patients can seriously compromise response to antiviral treatment. Therefore, our study was aimed at defining the prevalence of HBV drug-resistance in a population of 140 patients, all infected with HBV-D-genotype (the most common HBV-genotype in Eastern Europe, Mediterranean countries and Middle East) and naïve to antiviral therapy. HBV reverse-transcriptase (RT) region was sequenced and analyzed for 20 mutations, confirmed by in vitro studies as associated with resistance to nucleos(t)ide HBV-RT inhibitors (rtL80I/V-rtI169T-rtV173L-rtL180M-rtA181T/V/S-rtT184A/S/G/C-rtA194T-rtS202C/G/I-rtM204V/I-rtN236T-rtM250V). Amino acid changes at other six RT positions, potentially associated with resistance, were also analyzed (rtV84M-rtV191I-rtV207L-rtV214A-rtQ215S-rtI233V). Overall, only 2/140 (1.4%) patients carried primary drug-resistance mutations [rtA181V (0.7%), and rtA194T (0.7%)], while 3/140 (2.1%) patients harbored the secondary mutations rtV173L (1.4%) and rtL180M (0.7%). Additionally, five polymorphic mutations, with a suggested role in drug resistance, were detected [rtQ215S (12.8%), rtI233V (4.3%), rtV214A (3.6%), rtV191I (0.7%), rtV207L (0.7%)]. Notably, no YMDD mutations, namely rtM204V/I, were found. Taken together, the rate of important drug resistance mutations in naïve HBV D-genotype infected patients is today very low, and suggests the potential full efficacy of new-generation antiviral drugs used in first line therapy. Whether such low rate can be extrapolated to non HBV-D subtypes, requires a detailed investigation to be performed in a different cohort of patients.

Original languageEnglish
Pages (from-to)382-385
Number of pages4
JournalAntiviral Research
Volume92
Issue number2
DOIs
Publication statusPublished - Nov 2011

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Drug Resistance
Hepatitis B virus
Antiviral Agents
Genotype
Mutation
RNA-Directed DNA Polymerase
Eastern Europe
Reverse Transcriptase Inhibitors
Middle East
Therapeutics
Amino Acids
Pharmaceutical Preparations
Population

Keywords

  • D genotype
  • Drug resistance
  • Drug-naïve
  • HBV infection

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Characterization of drug-resistance mutations in HBV D-genotype chronically infected patients, naïve to antiviral drugs. / Salpini, R.; Svicher, V.; Cento, V.; Gori, C.; Bertoli, A.; Scopelliti, F.; Micheli, V.; Cappiello, T.; Spanò, A.; Rizzardini, G.; De Sanctis, G. M.; Sarrecchia, C.; Angelico, M.; Perno, C. F.

In: Antiviral Research, Vol. 92, No. 2, 11.2011, p. 382-385.

Research output: Contribution to journalArticle

Salpini, R, Svicher, V, Cento, V, Gori, C, Bertoli, A, Scopelliti, F, Micheli, V, Cappiello, T, Spanò, A, Rizzardini, G, De Sanctis, GM, Sarrecchia, C, Angelico, M & Perno, CF 2011, 'Characterization of drug-resistance mutations in HBV D-genotype chronically infected patients, naïve to antiviral drugs', Antiviral Research, vol. 92, no. 2, pp. 382-385. https://doi.org/10.1016/j.antiviral.2011.08.013
Salpini, R. ; Svicher, V. ; Cento, V. ; Gori, C. ; Bertoli, A. ; Scopelliti, F. ; Micheli, V. ; Cappiello, T. ; Spanò, A. ; Rizzardini, G. ; De Sanctis, G. M. ; Sarrecchia, C. ; Angelico, M. ; Perno, C. F. / Characterization of drug-resistance mutations in HBV D-genotype chronically infected patients, naïve to antiviral drugs. In: Antiviral Research. 2011 ; Vol. 92, No. 2. pp. 382-385.
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AU - Salpini, R.

AU - Svicher, V.

AU - Cento, V.

AU - Gori, C.

AU - Bertoli, A.

AU - Scopelliti, F.

AU - Micheli, V.

AU - Cappiello, T.

AU - Spanò, A.

AU - Rizzardini, G.

AU - De Sanctis, G. M.

AU - Sarrecchia, C.

AU - Angelico, M.

AU - Perno, C. F.

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N2 - Presence of drug-resistance mutations in drug-naïve hepatitis B virus (HBV) infected patients can seriously compromise response to antiviral treatment. Therefore, our study was aimed at defining the prevalence of HBV drug-resistance in a population of 140 patients, all infected with HBV-D-genotype (the most common HBV-genotype in Eastern Europe, Mediterranean countries and Middle East) and naïve to antiviral therapy. HBV reverse-transcriptase (RT) region was sequenced and analyzed for 20 mutations, confirmed by in vitro studies as associated with resistance to nucleos(t)ide HBV-RT inhibitors (rtL80I/V-rtI169T-rtV173L-rtL180M-rtA181T/V/S-rtT184A/S/G/C-rtA194T-rtS202C/G/I-rtM204V/I-rtN236T-rtM250V). Amino acid changes at other six RT positions, potentially associated with resistance, were also analyzed (rtV84M-rtV191I-rtV207L-rtV214A-rtQ215S-rtI233V). Overall, only 2/140 (1.4%) patients carried primary drug-resistance mutations [rtA181V (0.7%), and rtA194T (0.7%)], while 3/140 (2.1%) patients harbored the secondary mutations rtV173L (1.4%) and rtL180M (0.7%). Additionally, five polymorphic mutations, with a suggested role in drug resistance, were detected [rtQ215S (12.8%), rtI233V (4.3%), rtV214A (3.6%), rtV191I (0.7%), rtV207L (0.7%)]. Notably, no YMDD mutations, namely rtM204V/I, were found. Taken together, the rate of important drug resistance mutations in naïve HBV D-genotype infected patients is today very low, and suggests the potential full efficacy of new-generation antiviral drugs used in first line therapy. Whether such low rate can be extrapolated to non HBV-D subtypes, requires a detailed investigation to be performed in a different cohort of patients.

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