Virologic correlates of adherence to antiretroviral medications and therapeutic failure
Virologic correlates of adherence to antiretroviral medications and therapeutic failure
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DOI：
10.1097/00126334-200212153-00006
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发表时间：
2002-12-15
影响因子：
3.6
通讯作者：
Antinori, A
中科院分区：
文献类型：
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作者：
Perno, CF;Ceccherini-Silberstein, F;Antinori, A
坚持抗逆转录病毒治疗会影响抗病毒药物的药代动力学，并激活一系列事件，最终导致治疗成功或失败。最佳的粘附性通常提供最少的病毒复制和罕见的自发突变，由于野生型（更适合）毒株的竞争，这些突变无法固定在基因组中。因此，基于依从性的治疗成功大多伴随着野生型菌株的流行。在粘附性差的情况下，病毒复制是大量的，随机发生的突变往往被固定在基因组内。在这些条件下，突变耐药菌株将超过野生型病毒（对抗病毒药物敏感，因此无法与耐药菌株充分竞争细胞靶标）：因此，治疗失败发生，突变耐药菌株占主导地位。在粘附度非常低或没有粘附的情况下，会发生病毒学失败，尽管野生型病毒（其复制不受抗病毒药物的显著影响）不会被随机产生的突变株所取代，但无法在基因组中固定。综上所述，这些事件及其后果有力地支持了严格和持续监测抗逆转录病毒药物依从性的重要性，以防止发生通常对目前可用的大多数抗逆转录病毒药物产生交叉耐药的突变株的风险。
Adherence to antiretroviral therapy affects the pharmacokinetics of antiviral drugs and activates a cascade of events ultimately leading to therapeutic success or failure. An optimal adherence usually affords minimal rounds of virus replication and rare spontaneous mutations, which are unable to be fixed in the genome because of the competition of wild-type (more fit) strains. Therefore, adherence-based therapeutic success is mostly accompanied by the prevalence of wild-type strains. In case of poor adherence, virus replication is substantial, and mutations randomly occurring tend to be fixed within the genome. Under these conditions, mutated-resistant strains will outgrow wild-type virus (sensitive to antivirals and thereby unable to compete enough with resistant strains for cellular targets): thus, therapeutic failure occurs, and mutated resistant strains are predominant. In the case of very low or absent adherence, virologic failure occurs, although wild-type virus (whose replication is not significantly affected by antivirals) is not outgrown by mutated strains randomly produced but unable to be fixed within the genome. Taken together, these events and their consequences strongly support the relevance of a tight and continuous monitoring of adherence to antiretroviral drugs to prevent the risk of development of mutated strains often cross-resistant to the majority of antiretroviral drugs currently available.