Rapid decline in detectability of HIV-1 drug resistance mutations after stopping therapy
Rapid decline in detectability of HIV-1 drug resistance mutations after stopping therapy
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DOI：
10.1097/00002030-199912240-00001
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发表时间：
1999-12-24
期刊：
影响因子：
3.8
通讯作者：
Loveday, C
中科院分区：
文献类型：
--
作者：
Devereux, HL;Youle, M;Loveday, C
目的：要调查的耐药病毒的下降率后停止therapy.Design：25例患者接受多种联合治疗（平均5;范围3至9种药物）超过3个月的HIV-1耐药性治疗和关闭治疗进行了测试。停止治疗后6-175天的样本进行测试，停止therapeutic.Methods：患者进行了测试，基因型的变化与耐药性使用内部自动DNA测序检测耐药蛋白酶和逆转录酶genes.Results：所有样本测试时，患者治疗显示耐药性的证据（范围1-9突变）。按停药后时间分为3组：停药后< 2周，中位时间1.1周（A组）; 2周~ 2个月，中位时间6.4周（B组）;在治疗中检测到的原发突变（蛋白酶：30 N，46 I/L，82 A，90 M;逆转录酶：70 R，1841/V，225 Y/F）中，A组在停止治疗后100%保留; B组68%保留，C组15%保留。对于继发性突变，98%保留在A组中，99%保留在B组中，57%保留在C组中。结论：本研究显示，在停止联合治疗的13周内，大多数原发性突变的可检测性迅速下降。根据这些数据，只有在接受现有治疗或停止治疗< 2周时，才应进行HIV-1耐药性检测，以指导患者的治疗，前提是要做出与未来联合治疗有关的可靠决定。(C)1999年利平科特威廉姆斯&威尔金斯。
Objective: To investigate the rate of decline of drug resistant viruses after stopping therapy.Design: Twenty-five patients receiving multiple combination therapies (mean five; range three to nine drugs) for more than 3 months were tested for HIV-1 resistance on therapy and off therapy. The sample off therapy was tested 6-175 days after stopping therapy.Methods: Patients were tested for genotypic changes associated with drug resistance using an in-house automated DNA sequencing assay to detect resistance in the protease and reverse transcriptase genes.Results: All samples tested when patients were on therapy showed evidence of drug resistance (range 1-9 mutations). The patients were divided into three groups: < 2 weeks after stopping therapy, median 1.1 weeks (n = 8, group A); 2 weeks-2 months, median 6.4 weeks (n = 7, group B) and 2 months-6 months, median 12.9 weeks (n = 10, group C). Of primary mutations (protease: 30N, 46I/L 82A, 90M; reverse transcriptase: 70R, 1841/V, 225 Y/F) detected on therapy 100% remained after stopping therapy in group A; 68% remained in group B and 15% remained in group C. For secondary mutations 98% remained in group A; 99% remained in group B and 57% in group C.Conclusions: This study showed a rapid decline in detectability of the majority of primary mutations within 13 weeks of stopping combination therapy. From this data, HIV-1 resistance testing to direct patients' therapy should only be carried out when on existing therapy, or < 2 weeks off therapy, if reliable decisions are to be made relating to future combinations. (C) 1999 Lippincott Williams & Wilkins.