Paredes Roger, Tzou Philip L, van Zyl Gert, Barrow Geoff, Camacho Ricardo, Carmona Sergio, Grant Philip M, Gupta Ravindra K, Hamers Raph L, Harrigan P Richard, Jordan Michael R, Kantor Rami, Katzenstein David A, Kuritzkes Daniel R, Maldarelli Frank, Otelea Dan, Wallis Carole L, Schapiro Jonathan M, Shafer Robert W
IrsiCaixa AIDS Research Institute, Badalona, Spain.
Division of Infectious Diseases, Stanford University, Stanford, CA, United States of America.
PLoS One. 2017 Jul 28;12(7):e0181357. doi: 10.1371/journal.pone.0181357. eCollection 2017.
HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve.
An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations. The DRM pattern-ARV combinations included 52 nucleoside RT inhibitor (NRTI) DRM pattern-ARV combinations (13 patterns x 4 NRTIs), 27 nonnucleoside RT inhibitor (NNRTI) DRM pattern-ARV combinations (9 patterns x 3 NNRTIs), 39 protease inhibitor (PI) DRM pattern-ARV combinations (13 patterns x 3 PIs) and 42 integrase strand transfer inhibitor (INSTI) DRM pattern-ARV combinations (14 patterns x 3 INSTIs).
There was universal agreement that a GRT report should include the NRTIs lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir disoproxil fumarate; the NNRTIs efavirenz, etravirine, nevirapine, and rilpivirine; the PIs atazanavir/r, darunavir/r, and lopinavir/r (with "/r" indicating pharmacological boosting with ritonavir or cobicistat); and the INSTIs dolutegravir, elvitegravir, and raltegravir. There was a range of opinion as to whether the NRTIs stavudine and didanosine and the PIs nelfinavir, indinavir/r, saquinavir/r, fosamprenavir/r, and tipranavir/r should be included. The expert panel members provided highly concordant DRM pattern-ARV interpretations with only 6% of NRTI, 6% of NNRTI, 5% of PI, and 3% of INSTI individual expert interpretations differing from the expert panel median by more than one resistance level. The expert panel median differed from the HIVDB 7.0 GRT-IS for 20 (12.5%) of the 160 DRM pattern-ARV combinations including 12 NRTI, two NNRTI, and six INSTI pattern-ARV combinations. Eighteen of these differences were updated in HIVDB 8.1 GRT-IS to reflect the expert panel median. Additionally, HIVDB users are now provided with the option to exclude those ARVs not considered to be universally required.
The HIVDB GRT-IS was updated through a collaborative process to reflect changes in HIV drug resistance knowledge, treatment guidelines, and expert opinion. Such a process broadens consensus among experts and identifies areas requiring further study.
随着关于HIV-1耐药性的新研究发表以及治疗指南的演变，HIV-1基因型耐药性检测（GRT）解读系统（IS）需要更新。
成立了一个专家小组，为更新斯坦福HIV耐药数据库（HIVDB）的GRT-IS提供建议。就GRT报告中应包含的抗逆转录病毒药物（ARV）以及与160种耐药性突变（DRM）模式-ARV组合相关的耐药性解读对该小组进行了调查。DRM模式-ARV组合包括52种核苷类逆转录酶抑制剂（NRTI）DRM模式-ARV组合（13种模式×4种NRTI）、27种非核苷类逆转录酶抑制剂（NNRTI）DRM模式-ARV组合（9种模式×3种NNRTI）、39种蛋白酶抑制剂（PI）DRM模式-ARV组合（13种模式×3种PI）和42种整合酶链转移抑制剂（INSTI）DRM模式-ARV组合（14种模式×3种INSTI）。
普遍达成的共识是，GRT报告应包括NRTI中的拉米夫定、阿巴卡韦、齐多夫定、恩曲他滨和替诺福韦酯；NNRTI中的依非韦伦、依曲韦林、奈韦拉平和利匹韦林；PI中的阿扎那韦/利托那韦、达芦那韦/利托那韦和洛匹那韦/利托那韦（“/利托那韦”表示用利托那韦或考比司他进行药理学增效）；以及INSTI中的多替拉韦、埃替格韦和拉替拉韦。对于是否应包括NRTI中的司他夫定和去羟肌苷以及PI中的奈非那韦、茚地那韦/利托那韦、沙奎那韦/利托那韦、福沙普瑞那韦/利托那韦和替拉那韦/利托那韦，存在不同意见。专家小组成员提供了高度一致的DRM模式-ARV解读，只有6%的NRTI、6%的NNRTI、5%的PI和3%的INSTI个人专家解读与专家小组中位数的差异超过一个耐药水平。在160种DRM模式-ARV组合中，专家小组中位数与HIVDB 7.0 GRT-IS不同的有20种（12.5%），包括12种NRTI、2种NNRTI和6种INSTI模式-ARV组合。其中18种差异在HIVDB 8.1 GRT-IS中进行了更新，以反映专家小组中位数。此外，现在还为HIVDB用户提供了排除那些不被认为是普遍需要的ARV的选项。
通过合作过程对HIVDB GRT-IS进行了更新，以反映HIV耐药性知识、治疗指南和专家意见的变化。这样一个过程拓宽了专家之间的共识，并确定了需要进一步研究的领域。
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