Antiretroviral-drug resistance among patients recently infected with HIV
Antiretroviral-drug resistance among patients recently infected with HIV
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DOI：
10.1056/nejmoa013552
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发表时间：
2002-08-08
影响因子：
158.5
通讯作者：
Richman, DD
中科院分区：
文献类型：
--
作者：
Little, SJ;Holte, S;Richman, DD
背景在北美新近感染人类免疫缺陷病毒（HIV）的人群中，对抗逆转录病毒药物的传播性耐药的流行率估计为1%至11%。方法我们对治疗前抗逆转录病毒药物敏感性和药物敏感性进行了回顾性分析。在1995年5月至6月期间确定的377例尚未接受治疗的原发性HIV感染受试者的血浆样本中HIV耐药突变2000年在北美10个城市。对治疗的反应可以在202 subjects.Results超过五年的时间内，传播耐药的频率显着增加。对一种或多种药物的高水平耐药频率（受试者病毒的50%抑制浓度[IC 50]与药物敏感参考病毒的IC 50之比大于10）从1995年至1998年期间的3.4%增加到1999年至2000年期间的12.4多药耐药率从1.1%上升到6.2%（P = 0.01）。序列分析检测到的耐药突变频率从8.0%上升到22.7%（P < 0.001），多药耐药频率从3.8%上升到10.2%（P = 0.05）。在耐药病毒感染的受试者中，开始抗逆转录病毒治疗后的病毒抑制时间较长（P = 0.05），病毒学失败的时间较短（P = 0.05）。结论在北美，涉及耐药病毒的新发HIV感染的比例正在增加。最初的抗逆转录病毒治疗在感染耐药病毒的患者中更有可能失败。在治疗开始前进行耐药性测试，现在甚至对最近感染的患者也是如此。
Background Among persons in North America who are newly infected With the human immunodeficiency virus (HIV), the prevalence of transmitted resistance to antiretroviral drugs has been estimated at 1 to 11 percent.Methods We performed a retrospective analysis of susceptibility to antiretroviral drugs before treatment and drug-resistance mutations in HIV in plasma samples from 377 subjects with primary HIV infection who had not yet received treatment and who were identified between May 1995 and June 2000 in 10 North American cities. Responses to treatment could be evaluated in 202 subjects.Results Over the five-year period, the frequency of transmitted drug resistance increased significantly. The frequency of high-level resistance to one or more drugs (indicated by a value of more than 10 for the ratio of the 50 percent inhibitory concentration [IC50] for the subject's virus to the IC50 for a drug-sensitive reference virus) increased from 3.4 percent during the period from 1995 to 1998 to 12.4 percent during the period from 1999 to 2000 (P = 0.002), and the frequency of multidrug resistance increased from 1.1 percent to 6.2 percent (P = 0.01). The frequency of resistance mutations detected by sequence analysis increased from 8.0 percent to 22.7 percent (P < 0.001), and the frequency of multidrug resistance detected by sequence analysis increased from 3.8 percent to 10.2 percent (P = 0.05). Among subjects infected with drug-resistant virus, the time to viral suppression after the initiation of antiretroviral therapy was longer (P = 0.05), and the time to virologic failure was shorter (P = 0.05).Conclusions The proportion of new HIV infections that involve drug-resistant virus is increasing in North America. Initial antiretroviral therapy is more likely to fail in patients who are infected with drug-resistant virus. Testing for resistance to drugs before therapy begins is now indicated even for recently infected patients.