HIV-1 drug resistance in newly infected individuals
HIV-1 drug resistance in newly infected individuals
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DOI：
10.1001/jama.282.12.1135
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发表时间：
1999-09-22
影响因子：
120.7
通讯作者：
Markowitz, M
中科院分区：
文献类型：
--
作者：
Boden, D;Hurley, A;Markowitz, M
背景抗逆转录病毒药物治疗人类免疫缺陷病毒1型（HIV-1）感染的广泛使用可能导致耐药病毒传播的增加，这是一个值得关注的问题。使用逆转录酶聚合酶链反应衍生pol基因，随后对聚合酶链反应产物进行直接测序。1995年7月至1999年4月期间，80名受试者在感染HIV-1后平均1.7个月转介到Aaron Diamond AIDS研究中心，受试者来自大城市地区（65名来自纽约州纽约; 11名来自加利福尼亚州洛杉矶）; 60例（75%）为白色，和75主要结果测量已知耐药基因型的流行率和表型对个别抗病毒药物的敏感性降低。（16.3%）的基因型与任何抗逆转录病毒药物的耐药性。在10例受试者中发现了对任何核苷类逆转录酶抑制剂具有已知耐药突变的病毒，在6例受试者中发现了对任何非核苷类逆转录酶抑制剂具有已知耐药突变的病毒，在2例病例中发现了对任何蛋白酶抑制剂具有已知耐药突变的病毒。多重耐药病毒检出率为3.8%，蛋白酶基因多态性分布广泛。在67例病例中，基因型和表型的解释是一致的57例（85%），其中两项研究都performed. ConclusionThe流行率的HIV-1变异与已知的耐药基因型赋予任何抗逆转录病毒药物在这个队列的80个新感染的个人是16.3%。这些数据支持在原发性HIV-1感染的情况下扩大使用耐药性检测。应启动临床试验，以确定与使用经验性三联抗逆转录病毒治疗相比，耐药试验指导的治疗是否在治疗原发性HIV-1感染时提供额外的病毒学和免疫学益处。报告指出，应进一步努力扩大对耐药HIV-1变异体传播的研究，特别是在流行病学特征不同的人群中。
Context There is concern that the widespread use of antiretroviral drugs to treat human immunodeficiency virus 1 (HIV-1) infection may result in the increased transmission of drug-resistant virus.Objective To determine the prevalence of drug resistance-conferring mutations and phenotypic resistance to antiretroviral agents in a cohort of individuals newly infected with HIV-1.Design Case series with genetic analyses of the HIV-1 plasma-derived pol gene using reverse transcriptase polymerase chain reaction followed by direct sequencing of polymerase chain reaction products. Phenotypic analysis was performed with a recombinant virus assay.Setting and Patients Eighty individuals referred, on average, 1.7 months after infection with HIV-1 to the Aaron Diamond AIDS Research Center between July 1995 and April 1999, Subjects were from large urban areas (65 from New York, NY; 11 from Los Angeles, Calif); 60 (75%) were white, and 75 (93.8%) were homosexual men.Main Outcome Measures Prevalence of known resistance-conferring genotypes and reduced susceptibility to individual antiviral agents by phenotype.Results Thirteen individuals (16.3%) had genotypes associated with drug resistance to any antiretroviral agent. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors was found in 10 individuals, to any nonnucleoside reverse transcriptase inhibitors in 6 subjects, and to any protease inhibitors in 2 cases. Multidrug-resistant Virus was identified in 3 individuals (3.8%), Extensive polymorphism in the protease gene was identified. Interpretation of genotypes and phenotypes was concordant in 57 (85%) of the 67 cases in which both studies were performed.Conclusion The prevalence of HIV-1 variants with known resistance-conferring genotypes to any antiretroviral agent in this cohort of 80 newly infected individuals is 16.3%., These data support expanded use of resistance testing in the setting of primary HIV-1 infection. Clinical trials should be initiated to establish whether therapy guided by resistance testing, compared with the use of empirical tri pie combination antiretroviral therapy, provides additional virological and immunological benefit when treating primary HIV-1 infection. Further efforts to expand the study of transmission of drug-resistant HIV-1 variants, particularly in cohorts with different epidemiological profiles, are indicated.