title: Characterization of drug-resistance mutations in HBV D-genotype chronically infected patients, naïve to antiviral drugs.
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.
authors.affiliation: Department of Experimental Medicine and Biochemical Science, University of Tor Vergata, Via Montpellier 1, 00100 Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Salpini
authors.forename: V
authors.initials: V
authors.lastname: Svicher
authors.forename: V
authors.initials: V
authors.lastname: Cento
authors.forename: C
authors.initials: C
authors.lastname: Gori
authors.forename: A
authors.initials: A
authors.lastname: Bertoli
authors.forename: F
authors.initials: F
authors.lastname: Scopelliti
authors.forename: V
authors.initials: V
authors.lastname: Micheli
authors.forename: T
authors.initials: T
authors.lastname: Cappiello
authors.forename: A
authors.initials: A
authors.lastname: Spanò
authors.forename: G
authors.initials: G
authors.lastname: Rizzardini
authors.forename: G M
authors.initials: GM
authors.lastname: De Sanctis
authors.forename: C
authors.initials: C
authors.lastname: Sarrecchia
authors.forename: M
authors.initials: M
authors.lastname: Angelico
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D005061:Europe, Eastern; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D019083:Mediterranean Region; D008875:Middle Aged; D008877:Middle East; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D015995:Prevalence; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D014764:Viral Proteins; D012194:RNA-Directed DNA Polymerase