The prevalence of transmitted resistance to first-generation non-nucleoside reverse transcriptase inhibitors and its potential economic impact in HIV-infected patients.
The prevalence of transmitted resistance to first-generation non-nucleoside reverse transcriptase inhibitors and its potential economic impact in HIV-infected patients.
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DOI：
10.1371/journal.pone.0072784
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Stephens J
中科院分区：
文献类型：
--
作者：
Snedecor SJ;Khachatryan A;Nedrow K;Chambers R;Li C;Haider S;Stephens J
基于非核苷逆转录酶抑制剂（NNRTI）的高效抗逆转录病毒疗法（HAART），包括依非韦伦，被推荐为国际艾滋病指南的一线治疗选择，它是初始治疗中最常见的组成部分之一。在接受治疗和未接受治疗的艾滋病毒感染者中发现了对第一代nnrti的耐药性，这造成了依非韦伦对艾滋病毒感染者不完全有效的亚群。本分析回顾了已发表的文章和会议摘要，以检查欧洲、美国和加拿大第一代NNRTI耐药的流行情况，并确定耐药经济后果的已发表证据。据报道，NNRTI耐药性的流行率在美国/加拿大普遍高于欧洲，并且从20世纪90年代末到21世纪初，这两个地区的NNRTI耐药性都有所增加。最近基于时间的趋势表明，nnrti耐药流行率可能稳定或下降。这些耐药性估计值可能被低估了，因为使用超敏感基因型检测方法（识别标准检测方法未检测到的低频突变）的耐药性估计值显示，耐药性流行率增加了两倍以上。没有发现明确调查耐药性成本的研究。相反，大多数研究报告了治疗改变、失败或疾病进展的成本。在这些研究中，艾滋病毒感染者的年度艾滋病毒医疗费用增加1)随着CD4细胞减少，部分原因是住院时CD4细胞计数较低；2)治疗变化，3)每种病毒学失败。通过耐药传播或选择可能对疗效或治疗选择产生侵蚀，即使出现的频率较低，也可能成为使用第一代nnrti的障碍，而与方案失败和疾病进展相关的成本增加，表明了确定治疗耐药性以确保最佳初始治疗选择和方案继承的重要性。
Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) including efavirenz is recommended as a 1st-line treatment choice in international HIV guidelines, and it is one of the most common components of initial therapy. Resistance to 1st-generation NNRTIs is found among treated and untreated HIV-infected individuals creating a subpopulation of HIV-infected individuals in whom efavirenz is not fully effective. This analysis reviewed published articles and conference abstracts to examine the prevalence of 1st-generation NNRTI resistance in Europe, the United States (US), and Canada and to identify published evidence of the economic consequences of resistance. The reported prevalence of NNRTI resistance was generally higher in US/Canada than in Europe and increased in both regions from their introduction in the late 1990s until the early 2000s. The most recent time-based trends suggest that NNRTI-resistance prevalence may be stable or decreasing. These estimates of resistance may be understated as resistance estimates using ultra-sensitive genotypic testing methods, which identify low-frequency mutations undetected by standard testing methods, showed increased prevalence of resistance by more than two-fold. No studies were identified that explicitly investigated the costs of drug resistance. Rather, most studies reported costs of treatment change, failure, or disease progression. Among those studies, annual HIV medical costs of those infected with HIV increased 1) as CD4 cells decreased, driven in part by hospitalization at lower CD4 cell counts; 2) for treatment changes, and 3) for each virologic failure. The possible erosion of efficacy or of therapy choices through resistance transmission or selection, even when present with low frequency, may become a barrier to the use of 1st-generation NNRTIs and the increased costs associated with regimen failure and disease progression underlie the importance of identification of treatment resistance to ensure optimal initial therapy choice and regimen succession.
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