Nonnucleoside reverse transcriptase inhibitor phenotypic hypersusceptibility can be demonstrated in different assays.
Nonnucleoside reverse transcriptase inhibitor phenotypic hypersusceptibility can be demonstrated in different assays.
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非核苷类逆转录酶抑制剂的表型超敏性可以通过不同的测定来证明。
DOI：
10.1097/01.qai.0000159517.78100.7b
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Merigan,ThomasC
中科院分区：
文献类型：
--
作者：
Shulman,NancyS;Delgado,Jamael;Bosch,RonaldJ;Winters,MarkA;Johnston,Elizabeth;Shafer,RobertW;Katzenstein,DavidA;Merigan,ThomasC
Background:HIV-1 isolates harboring multiple nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations are more susceptible (“hypersusceptible”) to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) than isolates lacking NRTI resistance mutations, but this has only been reported with a single-cycle replication phenotypic assay. In fact, there was a report that a commercial multicycle assay did not readily detect hypersusceptibility.Objective:To see whether NNRTI hypersusceptibility can be demonstrated in other types of phenotypic assays, including multicycle assays and enzyme inhibition assays.Methods:The susceptibility of HIV-1 clones derived from different patients in multicycle assays was tested in peripheral blood mononuclear cells (PBMCs) and in an established cell line. In addition, the reverse transcriptase (RT) of many of these clones was expressed and their susceptibility tested in an RT inhibition assay. Nevirapine and efavirenz susceptibilities were tested and compared with a control wild-type virus or RT.Results:Hypersusceptibility to nevirapine and efavirenz was detected using each of the methods described above. R 2 values correlating the other methods with single-cycle assay values were between 0.66 and 0.96. In addition to the high correlations, the different methods gave similar numeric results.Conclusions:NNRTI hypersusceptibility is readily seen in multicycle susceptibility assays and in enzyme inhibition assays.The nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent antiretroviral agents that bind noncompetitively to a hydrophobic pocket in the reverse transcriptase (RT) enzyme close to the active site. 1 A potential limitation in using this class of antiretrovirals is that a single mutation in the RT enzyme NNRTI-binding pocket may confer high-level resistance to one or all of the available NNRTIs. 2, 3 Despite this low resistance barrier, the NNRTIs have been effective in durably suppressing HIV in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs) in both previously untreated HIV-infected patients 4-7 and NRTI-experienced patients 4-6 as well as or better than unboosted protease inhibitor-based regimens. 4, 5, 8
