Little Susan J, Holte Sarah, Routy Jean-Pierre, Daar Eric S, Markowitz Marty, Collier Ann C, Koup Richard A, Mellors John W, Connick Elizabeth, Conway Brian, Kilby Michael, Wang Lei, Whitcomb Jeannette M, Hellmann Nicholas S, Richman Douglas D
Antiviral Research Center, Department of Medicine, University of California-San Diego, San Diego 92103, USA.
N Engl J Med. 2002 Aug 8;347(6):385-94. doi: 10.1056/NEJMoa013552.
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.
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.
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).
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.
在北美新感染人类免疫缺陷病毒（HIV）的人群中，抗逆转录病毒药物传播耐药性的患病率估计为1%至11%。
我们对1995年5月至2000年6月期间在北美10个城市确诊的377例尚未接受治疗的原发性HIV感染患者血浆样本中治疗前抗逆转录病毒药物敏感性及HIV耐药突变进行了回顾性分析。对其中202例患者的治疗反应进行了评估。
在这五年期间，传播耐药性的频率显著增加。对一种或多种药物的高水平耐药频率（以患者病毒的50%抑制浓度[IC50]与药物敏感参考病毒的IC50之比大于10表示）从1995年至1998年期间的3.4%增至1999年至2000年期间的12.4%（P=0.002），多药耐药频率从1.1%增至6.2%（P=0.01）。通过序列分析检测到的耐药突变频率从8.0%增至22.7%（P<0.001），通过序列分析检测到的多药耐药频率从3.8%增至10.2%（P=0.05）。在感染耐药病毒的患者中，开始抗逆转录病毒治疗后病毒抑制的时间更长（P=0.05），病毒学失败的时间更短（P=0.05）。
在北美，涉及耐药病毒的新发HIV感染比例正在增加。感染耐药病毒的患者初始抗逆转录病毒治疗更易失败。现在即使对近期感染的患者也建议在开始治疗前进行耐药检测。
