12 薬 剤 耐 性 関 連 アミノ 酸 変 異 リストと 参 考 事 項 ( 表 1) 各 薬 剤 とそれに 対 する 薬 剤 耐 性 変 異 をまとめた 薬 剤 耐 性 変 異 リストがInternational Antiviral Society-USAよりほぼ 毎 年 更 新 報 告 されている [47a] 但 し この 表 では 耐 性 レベルの 評 価 は 考 慮 されていないことに 留 意 することが 必 要 である codon No A.A in wild type M A K D T K L F R/E/N R/E/N R/E/N R/E/N E codon No A.A in wild type M A K D T K L F A A L K K Y F E Q Y M Y G L T K C /I /I F codon No A.A in wild type M A K D T K L F A L K K Y F E Q Y M Y G L T K C L N R W Y/FQ/E L R/E/N N R W Y/F Q/E L N R W Y/F QE L ins R W Y/F Q/E R/E/N I L Y M I G L K K Y F E Q Y M Y G L T K C P I P N/S M I C/I L S/A H I P N/S A/M I C/I C/L/H A I E/H/P I A/G/K/Q D/F/T C/I/ S/A I E/P A/G/K/Q/R L C/I/ L Y codon No A.A in wild type L G K L D L E M K M I G I F I Q D I L I H A G T L N I I N L L I I/F//C E R/M/I/T/ I I I/F/ Q I/L/ I/L L L/Y L//M/T/A E L/M/ /I/T/L C/S/T/A A/T/F/I S M L/M I I F M/L P codon No A.A in wild type L G K L D L E M K M I G I F I Q D I L I I/R/ I /L /T S I/R/ M/R I I I I/L /T S/A F/I N I I/L /T F/I/R/ I I/L L//M S F/I/R/ M/R I I F I/L /A L /L/A/M/T/S P /T S F I/L/ T L A/M/ E K/R P H A G T L N I I I A/F/T/S I A/F/T I A/F/S/T A/F/S/T A/F/T/S L/T D D/S P P I/M/ F F F C M M M M M M M M L L L I/L N L L I codon No A.A in wild type T L E T F E G Y S Q N M Q A Y A/K A/S R/H/C H/K/R H I/A/K Q/C A Y G R/H/K H Y A/K S/A H codon No A.A in wild type G I Q Q N N D/S A/M/E R H T D 表 1 抗 HI-1 薬 剤 と 誘 導 される 耐 性 変 異 のまとめ (2013.Mar 版 IAS-USAを 元 にした) 12
18 参 考 文 献 1. Durant, J., et al., Drug-resistance genotyping in HI-1 therapy: the IRADAPT randomised controlled trial. Lancet, (9171): p Clevenbergh, P., et al., Persisting long-term benefit of genotype-guided treatment for HI-infected patients failing HAART. The iradapt Study: week 48 follow-up. Antivir Ther, (1): p Baxter, J.D., et al., A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS, (9): p. F Cingolani, A., et al., Usefulness of monitoring HI drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomized study (ARGENTA). AIDS, (3): p De Luca, A., et al., Three-year clinical outcomes of resistance genotyping and expert advice: extended follow-up of the Argenta trial. 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19 32. ergne, L., et al., HI-1 drug-resistance mutations among newly diagnosed patients before scaling-up programmes in Burkina Faso and Cameroon. Antivir Ther, (5): p Ndembi, N., et al., Transmitted antiretroviral drug resistance surveillance among newly HI type 1-diagnosed women attending an antenatal clinic in Entebbe, Uganda. AIDS Res Hum Retroviruses, (6): p Rodrigues, R., et al., Low prevalence of primary antiretroviral resistance mutations and predominance of HI-1 clade C at polymerase gene in newly diagnosed individuals from south Brazil. irus Res, (1-2): p Dilernia, D.A., et al., Drug-resistance surveillance among newly HI-1 diagnosed individuals in Buenos Aires, Argentina. AIDS, (10): p Kuritzkes, D.R., et al., Preexisting resistance to nonnucleoside reverse-transcriptase inhibitors predicts virologic failure of an efavirenz-based regimen in treatment-naive HI-1-infected subjects. J Infect Dis, (6): p Pillay, D., et al., The impact of transmitted drug resistance on the natural history of HI infection and response to firstline therapy. AIDS, (1): p Sax, P.E., et al., Should resistance testing be performed for treatment-naive HI-infected patients? A cost-effectiveness analysis. Clin Infect Dis, (9): p Nishizawa, M., et al., Highly-sensitive allele-specific PCR testing identifies a greater prevalence of transmitted HI drug resistance in Japan. PLoS One, (12): p. e Balduin, M., et al., Prevalence of minor variants of HI strains at reverse transcriptase position 103 in therapy-naive patients and their impact on the virological failure. J Clin irol, (1): p Metzner, K.J., et al., Minority quasispecies of drug-resistant HI-1 that lead to early therapy failure in treatment-naive and -adherent patients. Clin Infect Dis, (2): p Johnson, J.A., et al., Minority HI-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. PLoS Med, (7): p. e Little, S.J. and D.M. Smith, HI treatment decisions and transmitted drug resistance. Clin Infect Dis, (2): p 宮 崎 菜 穂 子 松 下 修 三 藤 井 毅 岩 本 愛 吉 杉 浦 亙, 多 剤 耐 性 症 例 治 療 を 目 的 とした 新 規 抗 HI 薬 使 用 症 例 に 対 する 緊 急 全 国 調 査, in 第 23 回 日 本 エイズ 学 会 学 術 集 会 総 会. 2009: 名 古 屋. 45. 宮 崎 菜 穂 子 杉 浦 亙, 我 が 国 における 抗 HI 治 療 と 多 剤 耐 性 症 例 の 現 状. IASR, : p Department of Health and Human Services Panel on antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HI-1-infected adults and adolescents a. Johnson,.A., et al., Update of the drug resistance mutations in HI-1: March Top Antivir Med, (1): p b. Ravela, J., et al., HI-1 protease and reverse transcriptase mutation patterns responsible for discordances between genotypic drug resistance interpretation algorithms. J Acquir Immune Defic Syndr, (1): p c. Snoeck, J., et al., Discordances between interpretation algorithms for genotypic resistance to protease and reverse transcriptase inhibitors of human immunodeficiency virus are subtype dependent. Antimicrob Agents Chemother, (2): p Sing, T., et al., Predicting HI coreceptor usage on the basis of genetic and clinical covariates. Antivir Ther, (7): p Hardy, W.D., et al., Two-year safety and virologic efficacy of maraviroc in treatment-experienced patients with CCR5- tropic HI-1 infection: 96-week combined analysis of MOTIATE 1 and 2. J Acquir Immune Defic Syndr, (5): p Saag, M., et al., A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-r5 HI-1. J Infect Dis, (11): p McGovern, R.A., et al., Population-based sequencing of the 3-loop can predict the virological response to maraviroc in treatment-naive patients of the MERIT trial. J Acquir Immune Defic Syndr, (3): p andekerckhove, L.P., et al., European guidelines on the clinical management of HI-1 tropism testing. Lancet Infect Dis, (5): p Jensen, M.A., et al., A reliable phenotype predictor for human immunodeficiency virus type 1 subtype C based on envelope 3 sequences. J irol, (10): p Jensen, M.A., et al., Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env 3 loop sequences. J irol, (24): p Poveda, E., et al., Design and validation of new genotypic tools for easy and reliable estimation of HI tropism before using CCR5 antagonists. J Antimicrob Chemother, (5): p Pillai, S., et al., A new perspective on 3 phenotype prediction. AIDS Res Hum Retroviruses, (2): p
HIV1 IAS-USA 1 HIV 1 Amino Acid, Wild-Type Primary Mutation Amino Acid Substitution M I 54 Secondary Mutation Codon Mutation Selected In Vitro MUTATIONS IN THE PROTEASE GENE SELECTED BY PROTEASE INHIBITORS
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