Transmission of HIV-1 Drug-Resistant Variants: Prevalence and Effect on Treatment Outcome
Transmission of HIV-1 Drug-Resistant Variants: Prevalence and Effect on Treatment Outcome
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DOI：
10.1086/650001
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发表时间：
2010-02-15
影响因子：
11.8
通讯作者：
Ostergaard, Lars
中科院分区：
文献类型：
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作者：
Jakobsen, Martin R.;Tolstrup, Martin;Ostergaard, Lars
背景人类免疫缺陷病毒1型（HIV-1）耐药性是抗逆转录病毒治疗（ART）全面成功的重要威胁。由于商业检测的灵敏度有限，可能低估了传播性耐药（TDR）;因此，需要研究TDR对治疗结果的影响。本研究的目的是调查TDR在HIV感染患者中的患病率，并通过分析血浆病毒RNA和外周血单核细胞前病毒DNA中耐药突变的存在来评估TDR与治疗结果的意义。在一项前瞻性研究中，我们通过比较敏感的多重引物延伸方法（称为HIV-SNaPshot）的结果，研究了61例患者的TDR水平，该方法能够筛选9种常见的核苷类逆转录酶抑制剂和非核苷酸类逆转录酶抑制剂突变，并与商业基因分型试剂盒ViroSeq（Abbott）的结果进行比较。22名患者被发现携带突变。通过HIV-SNaPshot检测确定的TDR患者多于通过ViroSeq分析确定的TDR患者（33% vs 13%; P = 0.015）。易感患者和携带低水平或高水平耐药突变的患者之间从开始ART到病毒学抑制的时间没有显著差异（平均值+/-标准差，128 +/- 59.1 vs 164.9 +/- 120.4; P = 0.147）。此外，在ART开始后1年，CD 4细胞计数分析显示两组间无显著差异（平均值为184 vs 219细胞/μ L; P = 0.267）。我们发现最近感染的ART初治患者中TDR的患病率高于单独通过ViroSeq基因分型估计的患病率。治疗开始后对患者的随访显示，携带TDR的患者有更多临床并发症的趋势，尽管无法证明对治疗结果的显著影响。因此，低丰度耐药准种在早期感染中的临床相关性仍存在疑问。
Background. 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.Methods. 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).Results. 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/mu L; P = .267).Conclusion. 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.