Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark.
Clin Infect Dis. 2010 Feb 15;50(4):566-73. doi: 10.1086/650001.
Human immunodeficiency virus type 1 (HIV-1) drug resistance is an important threat to the overall success of antiretroviral therapy (ART). Because of the limited sensitivity of commercial assays, transmitted drug resistance (TDR) may be underestimated; thus, the effect that TDR has on treatment outcome needs to be investigated. The objective of this study was to investigate the prevalence of TDR in HIV-infected patients and to evaluate the significance of TDR with respect to treatment outcome by analyzing plasma viral RNA and peripheral blood mononuclear cell proviral DNA for the presence of drug resistance mutations.
In a prospective study, we investigated the level of TDR in 61 patients by comparing the results of a sensitive multiplex-primer-extension approach (termed HIV-SNaPshot) that is capable of screening for 9 common nucleoside reverse-transcriptase inhibitor and nonnucleotide reverse-transcriptase inhibitor mutations with those of a commercial genotyping kit, ViroSeq (Abbott).
Twenty-two patients were found to carry mutations. More patients with TDR were identified by the HIV-SNaPshot assay than by ViroSeq analysis (33% vs 13%; [P=.015). There was no significant difference in the time from initiation of ART to virological suppression between susceptible patients and those carrying low- or high-level resistance mutations (mean +/- standard deviation, 128 +/- 59.1 vs 164.9 +/- 120.4; P=.147). Furthermore, analyses of CD4 cell counts showed no significant difference between these 2 groups 1 year after the initiation of ART (mean, 184 vs 219 cells/microL; P=.267).
We found the prevalence of TDR in recently infected ART-naive patients to be higher than that estimated by ViroSeq genotyping alone. Follow-up of patients after treatment initiation showed a trend toward there being more clinical complications for patients carrying TDR, although a significant effect on treatment outcome could not be demonstrated. Therefore, the clinical relevance of low-abundance resistant quasispecies in early infection is still in question.
人类免疫缺陷病毒 1 型（HIV-1）耐药性是抗逆转录病毒治疗（ART）全面成功的一个重要威胁。由于商业检测方法的敏感性有限，传播的耐药性（TDR）可能被低估；因此，需要研究 TDR 对治疗结果的影响。本研究的目的是调查 HIV 感染患者中 TDR 的流行情况，并通过分析血浆病毒 RNA 和外周血单个核细胞前病毒 DNA 中耐药突变的存在，评估 TDR 对治疗结果的意义。
在一项前瞻性研究中，我们通过比较一种敏感的多重引物延伸方法（称为 HIV-SNaPshot）的结果与商业基因分型试剂盒 ViroSeq（雅培）的结果，对 61 例患者的 TDR 水平进行了调查。该方法能够筛查 9 种常见的核苷逆转录酶抑制剂和非核苷逆转录酶抑制剂突变。
发现 22 例患者携带突变。通过 HIV-SNaPshot 检测发现携带 TDR 的患者比通过 ViroSeq 分析发现的患者多（33%比 13%；P=.015）。从开始接受 ART 到病毒学抑制的时间在敏感患者和携带低水平或高水平耐药突变的患者之间没有显著差异（平均+标准偏差，128+/-59.1 与 164.9+/-120.4；P=.147）。此外，ART 起始后 1 年的 CD4 细胞计数分析显示这两组之间没有显著差异（平均，184 与 219 个细胞/μL；P=.267）。
我们发现，新感染的、未经 ART 治疗的患者中 TDR 的流行率高于 ViroSeq 基因分型单独估计的流行率。对治疗开始后患者的随访显示，携带 TDR 的患者出现更多临床并发症的趋势，但不能证明对治疗结果有显著影响。因此，低丰度耐药准种在早期感染中的临床意义仍存在疑问。
