Is transmitted drug resistance in HIV on the rise? It seems so.
Is transmitted drug resistance in HIV on the rise? It seems so.
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HIV 传播的耐药性是否正在上升？
DOI：
10.1136/bmj.322.7294.1074
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Little,SJ
中科院分区：
文献类型：
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作者：
Little,SJ
HIV-1耐药变种的传播有可能严重限制新感染患者的治疗选择。在已经接受治疗的个人中选择艾滋病毒耐药变种也明显限制了药物治疗引起的病毒抑制的规模和持续时间。来自北美和欧洲的2份报告表明，多达14%的新近感染患者感染了一种病毒株，该病毒株具有良好的抗药性突变(1-10%的病例)或对特定药物的敏感性降低(2-14%的病例)。3-5目前还没有这些人群耐药传播的时间趋势，但英国在本周的《英国医学杂志》上发表的一篇论文表明，在1994年至2000年期间，感染耐药艾滋病毒病毒的风险有所增加(1087页)。6对传播可能性的估计取决于感染艾滋病毒的伴侣的暴露类型和病毒载量的大小。7对影响病毒传播的生物学因素的不完全了解进一步限制了对传播耐药性的预测估计的准确性。为了解释新近感染人群中耐药的相对患病率，我们必须考虑接触途径(粘膜或血液传播)、可能的地理变异、检测分析类型(v型表型)、敏感性阈值(表型分析)或考虑的突变类型(表型分析)，以及可能的HIV亚型(非BvBv重组亚型)。现有的检测方法一般只确定感染者体内主要病毒变种的抗药性。在没有药物选择压力的情况下，可能会发生回复到更具复制能力的、可能对药物敏感的变体，这反过来又可能排除对耐药变体的检测。因此，新感染患者中传播耐药的流行估计不应推广到尚未开始接受抗逆转录病毒药物治疗的已确定感染的患者，这些患者可能在存在药物选择压力的情况下，在存档的潜在病毒库中隐藏耐药变异。在英国监测艾滋病毒耐药性传播合作小组本周的研究中，对1994年至2000年期间出现艾滋病毒感染的69名受试者进行了感染后18个月内的耐药性评估；在耐药性测试时，没有人接受过抗逆转录病毒药物的治疗。6在14%的受试者中检测到基因耐药，3%的受试者突变导致对所有三种可用的抗逆转录病毒药物产生耐药性。这些估计与之前关于最近感染对象中传播的耐药性的报告一致。3-5这些研究人员还发现，在研究期间，传播耐药的流行率有所增加，在2000年发现的27%的受试者中发现了耐药变异。在同一时期，北美报告的传播性耐药流行率大幅上升。8传播耐药的临床重要性，特别是使用不同的敏感性阈值，尚未确定。然而，在已经确定接受治疗的患者中，耐药的基因型别和表型标记物与治疗的病毒学反应之间通常有良好的相关性。9.
The transmission of drug resistant variants of HIV-1 has the potential seriously to limit the therapeutic options of newly infected patients. The selection of HIV drug resistant variants among individuals who are already receiving treatment also clearly limits both the size and duration of the viral supression induced by drug treatment. 1 2 Reports from North America and Europe indicate that up to 14% of recently infected patients have been infected with a strain of virus bearing well characterised drug resistance mutations (in 1-10% of cases) or reduced susceptibility to a particular drug (2-14% of cases). 3–5 Temporal trends in the transmission of drug resistance for these populations are not yet available, but a paper from the United Kingdom in this week’s BMJ suggests an increase in the risk of being infected with drug resistant HIV virus between 1994 and 2000 (p 1087). 6 Estimates of the likelihood of transmission vary depending on the type of exposure and the magnitude of viral load in the HIV infected partner. 7 An incomplete understanding of the biological factors that influence viral transmission further limits the accuracy of projected estimates of transmitted drug resistance. In order to interpret the relative prevalence rates of drug resistance among recently infected subjects we must consider the route of exposure (mucosal or blood borne), possible geographical variations, detection assay type (genotype v phenotype), susceptibility threshold (for phenotypic assays) or type of mutations considered (for genotypic assays), and perhaps HIV subtype (non-B v B v recombinant subtypes). Available assays generally identify only the resistance profile of the predominant viral variant in the infected subject. In the absence of drug selection pressure, reversion to a more replication competent, perhaps drug susceptible, variant may occur, which may in turn preclude the detection of drug resistant variants. Prevalence estimates of transmitted drug resistance in newly infected patients should not therefore be generalised to patients with established infection who have not yet started treatment with antiretroviral drugs, who may harbour drug resistant variants within archived latent reservoirs of virus that may re-emerge in the presence of drug selection pressure.In the study this week from the UK Collaborative Group on Monitoring the Transmission of HIV Drug Resistance, 69 subjects who developed HIV infection during 1994–2000 were evaluated for resistance within 18 months of their infection; none had received treatment with antiretroviral drugs at the time of resistance testing. 6 Genotypic resistance was detected in 14% of the subjects, 3% with mutations conferring drug resistance to all three of the available classes of antiretroviral drugs. These estimates are consistent with previous reports of transmitted drug resistance in recently infected subjects. 3–5 These investigators also identified an increase in the prevalence of transmitted drug resistance during the period of study, with drug resistant variants detected in 27% of subjects identified in 2000. Significant increases in the prevalence of transmitted drug resistance have been reported from North America during this same period. 8 The clinical importance of transmitted drug resistance, particularly using different thresholds of susceptibility, has not been established. However, among patients already established on treatment there is generally good correlation between genotypic and phenotypic markers of resistance and virological responses to treatment. 9