Decreased bone mineral density (BMD) and osteoporotic fractures are areas of increasing concern among HIV-infected persons. Particular concern is the rapid decline in BMD after initiation of antiretroviral treatment (...Decreased bone mineral density (BMD) and osteoporotic fractures are areas of increasing concern among HIV-infected persons. Particular concern is the rapid decline in BMD after initiation of antiretroviral treatment (ART). This report describes DEXA-assessed changes in BMD and body fat in a study of fifteen antiretroviral-na?ve adults initiating abacavir/lamivudine and raltegravir for 96 weeks. Median percent changes from baseline at weeks 48 and 96 in BMD were 0.29% and -0.11% (spine);-1.25% and -1.75% (left hip). Median percent changes from baseline in fat from baseline were -0.82% and -3.04% (trunk);2.12% and 2.01% (limb). In this pilot study, ABC/3TC + RAL treatment had limited impact on BMD and body fat.展开更多
A selective and rapid high-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of raltegravir using raltegravir-d3 as an internal standard（IS）. The a...A selective and rapid high-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of raltegravir using raltegravir-d3 as an internal standard（IS）. The analyte and IS were extracted with methylene chloride and n-hexane solvent mixture from 100 mL human plasma. The chromatographic separation was achieved on a Chromolith RP-18 e endcapped C18（100 mm 4.6 mm） column in a run time of 2.0 min. Quantitation was performed in the negative ionization mode using the transitions of m/z 443.1-316.1 for raltegravir and m/z 446.1-319.0 for IS. The linearity of the method was established in the concentration range of 2.0–6000 ng/m L.The mean extraction recovery for raltegravir and IS was 92.6% and 91.8%, respectively, and the IS-normalized matrix factors for raltegravir ranged from 0.992 to 0.999. The application of this method was demonstrated by a bioequivalence study on 18 healthy subjects.展开更多
目的探究整合酶的分子耐药机制。方法研究采用Discovery Studio 2.5软件模块的分子对接程序,构建整合酶药物雷特格韦(Raltegravir,RAL)与整合酶核心区蛋白晶体结构(1BL3)的复合物模型,并结合已知的整合酶耐药突变位点Q148H、N155H、Y143...目的探究整合酶的分子耐药机制。方法研究采用Discovery Studio 2.5软件模块的分子对接程序,构建整合酶药物雷特格韦(Raltegravir,RAL)与整合酶核心区蛋白晶体结构(1BL3)的复合物模型,并结合已知的整合酶耐药突变位点Q148H、N155H、Y143C和其他野生型残基突变(T97A、A128T、E138K、E157Q、G163R),构建一系列整合酶蛋白耐药基因突变体。以此进一步计算艾滋病病毒Ⅰ型(HIV-1)整合酶蛋白发生氨基酸残基突变后,与雷特格韦之间分子自由能的改变,并分析雷特格韦与不同整合酶蛋白耐药基因突变体之间的结合自由能。结果主要突变Q148H、N155H、Y143C均位于RAL与整合酶的活性中心,均可明显改变雷特格韦与核心区晶体之间的结合自由能,以N155H改变最为明显,其次为Q148H、Y143C。此外,野生型基因突变也造成一定程度的自由能改变,具有一定的耐药性意义。结论证实耐药位点突变导致整合酶蛋白与雷特格韦之间结合自由能增大,影响药物与整合酶的结合。展开更多
目的利用已建立的整合酶晶体结构与整合酶抑制剂雷特格韦的分子对接模型,计算HIV-1整合酶突变蛋白体与雷特格韦之间分子自由能的改变,以此评估整合酶基因突变是否会造成针对雷特格韦的耐药性。方法本研究采用Discovery Studio 2.5软件...目的利用已建立的整合酶晶体结构与整合酶抑制剂雷特格韦的分子对接模型,计算HIV-1整合酶突变蛋白体与雷特格韦之间分子自由能的改变,以此评估整合酶基因突变是否会造成针对雷特格韦的耐药性。方法本研究采用Discovery Studio 2.5软件模块的分子对接程序构建整合酶药物雷特格韦与整合酶核心区蛋白晶体结构(1BL3)的复合物模型,采用氨基酸突变的方式进入整合酶野生型蛋白突变体,计算整合酶蛋白与雷特格韦分子间结合自由能。结果与1BL3整合酶蛋白结构相比,分别携带K14R、V31I、V54I,I72V、I84M,T112V、T124A、T125A、G134N、I135V、K136R、D167E、G193E、V201I、L203I氨基酸突变的整合酶蛋白与雷特格韦之间未见明显分子间结合自由能改变。引入已知耐药基因突变N155H,Q148H,Y143C的整合酶结构可造成彼此间分子自由能的明显提高。结论分子模拟技术建立雷特格韦与整合酶蛋白耐药性预测模型,完成了整合酶野生型蛋白结构与雷特格韦之间结合自由能计算和耐药性分析。我国HIV-1整合酶流行株对雷特格韦敏感,不存在耐药性。展开更多
Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patient...Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patients with chronic virologic failure. Methods: We conducted a descriptive analysis of the immuno-virologic responses in HIV-1 adult infected patients: 1) harbouring multiple therapeutic failures with ART;2) with no virologic response obtained over 10 years (1997-2008);and 3) treated with OBT combined with new drugs including at least 1 of the 3 active ART among darunavir/ritonavir, etravirine and raltegravir;4) observed between month 0 (M0), before new ART to month 12 (M12) after new ART initialisation. Results: Twenty three patients were included in the study. After OBT, the proportion of patients with undetectable viral load was significantly higher at M6 and M12 than M0 (86% and 73% versus 0%, p = 0.03, respectively). At the same period, the median HIV viral load decreased significantly in 19/23 (83%) patients from 4.3 to 1.69log10 HIV-1 RNA copies/ml (p 3 [0 - 604] to 449/mm3 [130 - 964] between M0 and M12 (p 3 decreased from 57% to 23% (p = 0.02). Tolerability was good and no death was recorded during the 12-month' follow-up. Conclusions: These results show that the combination of OBT with the new ART can offer a salvage therapy in patients presenting a long-term history of virologic failures.展开更多
文摘Decreased bone mineral density (BMD) and osteoporotic fractures are areas of increasing concern among HIV-infected persons. Particular concern is the rapid decline in BMD after initiation of antiretroviral treatment (ART). This report describes DEXA-assessed changes in BMD and body fat in a study of fifteen antiretroviral-na?ve adults initiating abacavir/lamivudine and raltegravir for 96 weeks. Median percent changes from baseline at weeks 48 and 96 in BMD were 0.29% and -0.11% (spine);-1.25% and -1.75% (left hip). Median percent changes from baseline in fat from baseline were -0.82% and -3.04% (trunk);2.12% and 2.01% (limb). In this pilot study, ABC/3TC + RAL treatment had limited impact on BMD and body fat.
文摘A selective and rapid high-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of raltegravir using raltegravir-d3 as an internal standard（IS）. The analyte and IS were extracted with methylene chloride and n-hexane solvent mixture from 100 mL human plasma. The chromatographic separation was achieved on a Chromolith RP-18 e endcapped C18（100 mm 4.6 mm） column in a run time of 2.0 min. Quantitation was performed in the negative ionization mode using the transitions of m/z 443.1-316.1 for raltegravir and m/z 446.1-319.0 for IS. The linearity of the method was established in the concentration range of 2.0–6000 ng/m L.The mean extraction recovery for raltegravir and IS was 92.6% and 91.8%, respectively, and the IS-normalized matrix factors for raltegravir ranged from 0.992 to 0.999. The application of this method was demonstrated by a bioequivalence study on 18 healthy subjects.
文摘目的探究整合酶的分子耐药机制。方法研究采用Discovery Studio 2.5软件模块的分子对接程序,构建整合酶药物雷特格韦(Raltegravir,RAL)与整合酶核心区蛋白晶体结构(1BL3)的复合物模型,并结合已知的整合酶耐药突变位点Q148H、N155H、Y143C和其他野生型残基突变(T97A、A128T、E138K、E157Q、G163R),构建一系列整合酶蛋白耐药基因突变体。以此进一步计算艾滋病病毒Ⅰ型(HIV-1)整合酶蛋白发生氨基酸残基突变后,与雷特格韦之间分子自由能的改变,并分析雷特格韦与不同整合酶蛋白耐药基因突变体之间的结合自由能。结果主要突变Q148H、N155H、Y143C均位于RAL与整合酶的活性中心,均可明显改变雷特格韦与核心区晶体之间的结合自由能,以N155H改变最为明显,其次为Q148H、Y143C。此外,野生型基因突变也造成一定程度的自由能改变,具有一定的耐药性意义。结论证实耐药位点突变导致整合酶蛋白与雷特格韦之间结合自由能增大,影响药物与整合酶的结合。
文摘目的利用已建立的整合酶晶体结构与整合酶抑制剂雷特格韦的分子对接模型,计算HIV-1整合酶突变蛋白体与雷特格韦之间分子自由能的改变,以此评估整合酶基因突变是否会造成针对雷特格韦的耐药性。方法本研究采用Discovery Studio 2.5软件模块的分子对接程序构建整合酶药物雷特格韦与整合酶核心区蛋白晶体结构(1BL3)的复合物模型,采用氨基酸突变的方式进入整合酶野生型蛋白突变体,计算整合酶蛋白与雷特格韦分子间结合自由能。结果与1BL3整合酶蛋白结构相比,分别携带K14R、V31I、V54I,I72V、I84M,T112V、T124A、T125A、G134N、I135V、K136R、D167E、G193E、V201I、L203I氨基酸突变的整合酶蛋白与雷特格韦之间未见明显分子间结合自由能改变。引入已知耐药基因突变N155H,Q148H,Y143C的整合酶结构可造成彼此间分子自由能的明显提高。结论分子模拟技术建立雷特格韦与整合酶蛋白耐药性预测模型,完成了整合酶野生型蛋白结构与雷特格韦之间结合自由能计算和耐药性分析。我国HIV-1整合酶流行株对雷特格韦敏感,不存在耐药性。
文摘Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patients with chronic virologic failure. Methods: We conducted a descriptive analysis of the immuno-virologic responses in HIV-1 adult infected patients: 1) harbouring multiple therapeutic failures with ART;2) with no virologic response obtained over 10 years (1997-2008);and 3) treated with OBT combined with new drugs including at least 1 of the 3 active ART among darunavir/ritonavir, etravirine and raltegravir;4) observed between month 0 (M0), before new ART to month 12 (M12) after new ART initialisation. Results: Twenty three patients were included in the study. After OBT, the proportion of patients with undetectable viral load was significantly higher at M6 and M12 than M0 (86% and 73% versus 0%, p = 0.03, respectively). At the same period, the median HIV viral load decreased significantly in 19/23 (83%) patients from 4.3 to 1.69log10 HIV-1 RNA copies/ml (p 3 [0 - 604] to 449/mm3 [130 - 964] between M0 and M12 (p 3 decreased from 57% to 23% (p = 0.02). Tolerability was good and no death was recorded during the 12-month' follow-up. Conclusions: These results show that the combination of OBT with the new ART can offer a salvage therapy in patients presenting a long-term history of virologic failures.
