PMID- 21920388 OWN - NLM STAT- MEDLINE DCOM- 20120208 LR - 20111025 IS - 1872-9096 (Electronic) IS - 0166-3542 (Linking) VI - 92 IP - 2 DP - 2011 Nov TI - Characterization of drug-resistance mutations in HBV D-genotype chronically infected patients, naive to antiviral drugs. PG - 382-5 LID - 10.1016/j.antiviral.2011.08.013 [doi] AB - Presence of drug-resistance mutations in drug-naive 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 naive 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 naive 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. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Salpini, R AU - Salpini R AD - Department of Experimental Medicine and Biochemical Science, University of Tor Vergata, Via Montpellier 1, 00100 Rome, Italy. FAU - Svicher, V AU - Svicher V FAU - Cento, V AU - Cento V FAU - Gori, C AU - Gori C FAU - Bertoli, A AU - Bertoli A FAU - Scopelliti, F AU - Scopelliti F FAU - Micheli, V AU - Micheli V FAU - Cappiello, T AU - Cappiello T FAU - Spano, A AU - Spano A FAU - Rizzardini, G AU - Rizzardini G FAU - De Sanctis, G M AU - De Sanctis GM FAU - Sarrecchia, C AU - Sarrecchia C FAU - Angelico, M AU - Angelico M FAU - Perno, C F AU - Perno CF LA - eng SI - GENBANK/JN225963 SI - GENBANK/JN225964 SI - GENBANK/JN225965 SI - GENBANK/JN225966 SI - GENBANK/JN225967 SI - GENBANK/JN225968 SI - GENBANK/JN225969 SI - GENBANK/JN225970 SI - GENBANK/JN225971 SI - GENBANK/JN225972 SI - GENBANK/JN225973 SI - GENBANK/JN225974 SI - GENBANK/JN225975 SI - GENBANK/JN225976 SI - GENBANK/JN225977 SI - GENBANK/JN225978 SI - GENBANK/JN225979 SI - GENBANK/JN225980 SI - GENBANK/JN225981 SI - GENBANK/JN225982 SI - GENBANK/JN225983 SI - GENBANK/JN225984 SI - GENBANK/JN225985 SI - GENBANK/JN225986 SI - GENBANK/JN225987 SI - GENBANK/JN225988 SI - GENBANK/JN225989 SI - GENBANK/JN225990 SI - GENBANK/JN225991 SI - GENBANK/JN225992 SI - GENBANK/JN225993 SI - GENBANK/JN225994 SI - GENBANK/JN225995 SI - GENBANK/JN225996 SI - GENBANK/JN225997 SI - GENBANK/JN225998 SI - GENBANK/JN225999 SI - GENBANK/JN226000 SI - GENBANK/JN226001 SI - GENBANK/JN226002 SI - GENBANK/JN226003 SI - GENBANK/JN226004 SI - GENBANK/JN226005 SI - GENBANK/JN226006 SI - GENBANK/JN226007 SI - GENBANK/JN226008 SI - GENBANK/JN226009 SI - GENBANK/JN226010 SI - GENBANK/JN226011 SI - GENBANK/JN226012 SI - GENBANK/JN226013 SI - GENBANK/JN226014 SI - GENBANK/JN226015 SI - GENBANK/JN226016 SI - GENBANK/JN226017 SI - GENBANK/JN226018 SI - GENBANK/JN226019 SI - GENBANK/JN226020 SI - GENBANK/JN226021 SI - GENBANK/JN226022 SI - GENBANK/JN226023 SI - GENBANK/JN226024 SI - GENBANK/JN226025 SI - GENBANK/JN226026 SI - GENBANK/JN226027 SI - GENBANK/JN226028 SI - GENBANK/JN226029 SI - GENBANK/JN226030 SI - GENBANK/JN226031 SI - GENBANK/JN226032 SI - GENBANK/JN226033 SI - GENBANK/JN226034 SI - GENBANK/JN226035 SI - GENBANK/JN226036 SI - GENBANK/JN226037 SI - GENBANK/JN226038 SI - GENBANK/JN226039 SI - GENBANK/JN226040 SI - GENBANK/JN226041 SI - GENBANK/JN226042 SI - GENBANK/JN226043 SI - GENBANK/JN226044 SI - GENBANK/JN226045 SI - GENBANK/JN226046 SI - GENBANK/JN226047 SI - GENBANK/JN226048 SI - GENBANK/JN226049 SI - GENBANK/JN226050 SI - GENBANK/JN226051 SI - GENBANK/JN226052 SI - GENBANK/JN226053 SI - GENBANK/JN226054 SI - GENBANK/JN226055 SI - GENBANK/JN226056 SI - GENBANK/JN226057 SI - GENBANK/JN226058 SI - GENBANK/JN226059 SI - GENBANK/JN226060 SI - GENBANK/JN226061 SI - GENBANK/JN226062 SI - GENBANK/JN226063 SI - GENBANK/JN226064 SI - GENBANK/JN226065 SI - GENBANK/JN226066 SI - GENBANK/JN226067 SI - GENBANK/JN226068 SI - GENBANK/JN226069 SI - GENBANK/JN226070 SI - GENBANK/JN226071 SI - GENBANK/JN226072 SI - GENBANK/JN226073 SI - GENBANK/JN226074 SI - GENBANK/JN226075 SI - GENBANK/JN226076 SI - GENBANK/JN226077 SI - GENBANK/JN226078 SI - GENBANK/JN226079 SI - GENBANK/JN226080 SI - GENBANK/JN226081 SI - GENBANK/JN226082 SI - GENBANK/JN226083 SI - GENBANK/JN226084 SI - GENBANK/JN226085 SI - GENBANK/JN226086 SI - GENBANK/JN226087 SI - GENBANK/JN226088 SI - GENBANK/JN226089 SI - GENBANK/JN226090 SI - GENBANK/JN226091 SI - GENBANK/JN226092 SI - GENBANK/JN226093 SI - GENBANK/JN226094 SI - GENBANK/JN226095 SI - GENBANK/JN226096 SI - GENBANK/JN226097 SI - GENBANK/JN226098 SI - GENBANK/JN226099 PT - Journal Article DEP - 20110905 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antiviral Agents) RN - 0 (DNA, Viral) RN - 0 (Viral Proteins) RN - EC 2.7.7.49 (RNA-Directed DNA Polymerase) SB - IM MH - Adult MH - Amino Acid Substitution MH - Antiviral Agents/*pharmacology MH - DNA Mutational Analysis MH - DNA, Viral/chemistry/genetics MH - *Drug Resistance, Viral MH - Europe, Eastern MH - Genotype MH - Hepatitis B virus/classification/*drug effects/genetics/*isolation & purification MH - Hepatitis B, Chronic/*virology MH - Humans MH - Mediterranean Region MH - Middle Aged MH - Middle East MH - Molecular Sequence Data MH - *Mutation, Missense MH - Prevalence MH - RNA-Directed DNA Polymerase/genetics MH - Sequence Analysis, DNA MH - Viral Proteins/genetics EDAT- 2011/09/17 06:00 MHDA- 2012/02/09 06:00 CRDT- 2011/09/17 06:00 PHST- 2011/03/31 00:00 [received] PHST- 2011/07/12 00:00 [revised] PHST- 2011/08/16 00:00 [accepted] PHST- 2011/09/17 06:00 [entrez] PHST- 2011/09/17 06:00 [pubmed] PHST- 2012/02/09 06:00 [medline] AID - S0166-3542(11)00414-1 [pii] AID - 10.1016/j.antiviral.2011.08.013 [doi] PST - ppublish SO - Antiviral Res. 2011 Nov;92(2):382-5. doi: 10.1016/j.antiviral.2011.08.013. Epub 2011 Sep 5.