Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, 50935 Cologne, Germany.
Med Microbiol Immunol. 2011 Nov;200(4):225-32. doi: 10.1007/s00430-011-0194-1. Epub 2011 Apr 8.
The SnoB study analysed the variability of the integrase (IN) gene of non-B viruses from treatment-naïve patients to determine whether non-B subtypes carry natural resistance mutations to raltegravir (RAL). Plasma viral RNA from 427 patients was gained, and IN sequences were subtyped and screened for subtype-specific highly-variable residues. Seven viruses of different subtypes were phenotypically tested for RAL susceptibility; 359/427 samples could be sequenced. One hundred and seventy samples (47%) were classified as non-B subtypes. No primary RAL resistance-associated mutations (RRAMs) were detected. Certain secondary mutations were found, mostly related to specific non-B subtypes. L74 M was significantly more prevalent in subtype 02_AG, T97A in A and 06_cpx, V151I in 06_cpx, and G163R in 12_BF. Various additional mutations were also detected and could be associated with the subtype too. While K156 N and S230 N were correlated with B subtype, V72I, L74I, T112I, T125A, V201I and T206S were more frequent in certain non-B subtypes. The resistance factors (RF) of 7 viral strains of different subtypes ranged from 1.0 to 1.9. No primary or secondary but subtype-associated additional RRAMs were present. No correlation between RF and additional RRAMs was found. The prevalence of RRAMs was higher in non-B samples. However, the RFs for the analysed non-B subtypes showed lower values to those reported relevant to clinical failure. As the role of baseline secondary and additional mutations on RAL therapy failure is actually not known, baseline IN screening is necessary.
SnoB 研究分析了未经治疗的患者中非 B 型病毒整合酶（IN）基因的变异性，以确定非 B 亚型是否对拉替拉韦（RAL）具有天然耐药突变。从 427 例患者中获得血浆病毒 RNA，并对 IN 序列进行亚分型和筛选，以寻找亚型特异性高度变异残基。对 7 种不同亚型的病毒进行 RAL 敏感性表型检测；对 427 个样本中的 359 个进行了测序。170 个样本（47%）被归类为非 B 亚型。未检测到原发性 RAL 耐药相关突变（RRAMs）。发现了某些次要突变，主要与特定的非 B 亚型有关。L74M 在 02_AG 亚型中更为常见，T97A 在 A 和 06_cpx 中，V151I 在 06_cpx 中，G163R 在 12_BF 中。还检测到了各种其他突变，也可能与亚型有关。虽然 K156N 和 S230N 与 B 亚型相关，但 V72I、L74I、T112I、T125A、V201I 和 T206S 在某些非 B 亚型中更为常见。不同亚型的 7 株病毒的耐药因子（RF）范围为 1.0 至 1.9。未发现原发性或继发性但与亚型相关的额外 RRAMs。未发现 RF 与额外 RRAMs 之间存在相关性。非 B 样本中的 RRAMs 患病率较高。然而，分析的非 B 亚型的 RF 值低于与临床失败相关的报告值。由于基线次要和额外突变对 RAL 治疗失败的作用实际上并不清楚，因此需要进行基线 IN 筛查。
