Hirsch M S, Conway B, D'Aquila R T, Johnson V A, Brun-Vézinet F, Clotet B, Demeter L M, Hammer S M, Jacobsen D M, Kuritzkes D R, Loveday C, Mellors J W, Vella S, Richman D D
Harvard Medical School, Boston, MA, USA.
JAMA. 1998 Jun 24;279(24):1984-91. doi: 10.1001/jama.279.24.1984.
To review current knowledge of the biology and clinical implications of human immunodeficiency virus (HIV) resistance to antiretroviral drugs, describe assays for measuring resistance, and assess their use in clinical practice.
The International AIDS Society-USA assembled a panel of 13 physicians with expertise in basic science, clinical research, and patient care relevant to HIV resistance to antiretroviral drugs.
We reviewed available data from published reports and presented at national and international research conferences. Basic science research, clinical trial results, and expert opinions were used to form the basis of this report. Data on methods for and characteristics of specific genotypic and phenotypic assays were obtained from manufacturers and service providers.
The panel met regularly between October 1997 and April 1998. Panel subgroups developed and discussed different sections of the report before discussing them with the entire panel. Conclusions and suggested approaches to the use of resistance testing were determined by group consensus.
Plasma HIV RNA level and CD4+ cell count are the primary values that should be used to guide the initiation of antiretroviral therapy and subsequent changes in therapy. Possible causes of treatment failure other than development of drug resistance that should be considered are adherence, drug potency, and pharmacokinetic issues. Genotypic and phenotypic testing for HIV resistance to antiretroviral drugs may prove useful for individual patient management. Assays under development need validation, standardization, and a clearer definition of their clinical roles. Possible current roles of resistance testing for choosing an initial regimen or changing antiretroviral therapy, as well as possible implications of the presence or absence of phenotypic resistance and genotypic changes, are discussed.
回顾关于人类免疫缺陷病毒（HIV）对抗逆转录病毒药物耐药性的生物学及临床意义的现有知识，描述耐药性检测方法，并评估其在临床实践中的应用。
美国国际艾滋病协会召集了一个由13名医生组成的小组，这些医生在与HIV对抗逆转录病毒药物耐药性相关的基础科学、临床研究及患者护理方面具有专业知识。
我们回顾了已发表报告以及在国内和国际研究会议上展示的可用数据。基础科学研究、临床试验结果及专家意见构成了本报告的基础。关于特定基因型和表型检测方法及特征的数据来自制造商和服务提供商。
该小组在1997年10月至1998年4月期间定期开会。小组亚组在与整个小组讨论之前先制定并讨论了报告的不同部分。耐药性检测使用的结论和建议方法由小组共识确定。
血浆HIV RNA水平和CD4 +细胞计数是应指导抗逆转录病毒治疗启动及后续治疗调整的主要指标。除耐药性产生外，应考虑的治疗失败的可能原因包括依从性、药物效力和药代动力学问题。针对HIV对抗逆转录病毒药物的耐药性进行基因型和表型检测可能对个体患者管理有用。正在研发的检测方法需要验证、标准化，并更明确地界定其临床作用。讨论了耐药性检测在选择初始治疗方案或改变抗逆转录病毒治疗方面可能的当前作用，以及表型耐药性和基因型变化存在或不存在的可能影响。
