Sichtig Nadine, Sierra Saleta, Kaiser Rolf, Däumer Martin, Reuter Stefan, Schülter Eugen, Altmann Andre, Fätkenheuer Gerd, Dittmer Ulf, Pfister Herbert, Esser Stefan
Institute of Virology, University of Cologne, Germany.
J Antimicrob Chemother. 2009 Jul;64(1):25-32. doi: 10.1093/jac/dkp153. Epub 2009 May 14.
We investigated the prevalence of raltegravir resistance-associated mutations at baseline and their evolution during raltegravir therapy in patients infected with different HIV-1 subtypes.
At pre-treatment screening, the integrase gene from plasma samples from patients infected with subtype B and non-B viruses was analysed. Raltegravir resistance evolution was further evaluated in 10 heavily pre-treated patients.
Two hundred and nine plasma samples from 94 subtype B and 115 non-B patients were sequenced. No signature/primary raltegravir resistance mutations were detected at baseline. The secondary mutations L74M, T97A, V151I and G163R were observed with a frequency of <4%. The primary mutations N155H, Q148R/H or Q143R were observed during raltegravir therapy. The Q148R/H was detected only in subtype B. A switch of the primary mutation during raltegravir treatment was not restricted to the subtype B viruses. The prevalence of each primary mutation varied depending on the length of the raltegravir therapy. The Q148R/H was mostly detected after short exposure to raltegravir, while the Y143R was observed only after prolonged raltegravir exposure. We detected an association between the presence of the T206S in the baseline genotype and the absence of the primary Q148R/H mutation or any secondary mutation accompanying the N155H following raltegravir failure.
A number of secondary and additional mutations were found in baseline genotypes. During therapy, when the virus was not optimally suppressed, resistance mutations developed, which were dependent on subtype and time on raltegravir.
我们调查了不同HIV-1亚型感染患者基线时拉替拉韦耐药相关突变的流行情况及其在拉替拉韦治疗期间的演变。
在治疗前筛查时，分析了感染B亚型和非B亚型病毒患者血浆样本中的整合酶基因。对10例接受过大量前期治疗的患者进一步评估了拉替拉韦耐药性的演变。
对94例B亚型和115例非B亚型患者的209份血浆样本进行了测序。基线时未检测到特征性/原发性拉替拉韦耐药突变。观察到继发性突变L74M、T97A、V151I和G163R，频率<4%。在拉替拉韦治疗期间观察到原发性突变N155H、Q148R/H或Q143R。仅在B亚型中检测到Q148R/H。拉替拉韦治疗期间原发性突变的转换并不局限于B亚型病毒。每种原发性突变的流行率因拉替拉韦治疗时间的长短而异。Q148R/H大多在短期接触拉替拉韦后检测到，而Y143R仅在长期接触拉替拉韦后观察到。我们检测到基线基因型中存在T206S与拉替拉韦治疗失败后原发性Q148R/H突变缺失或伴随N155H的任何继发性突变缺失之间存在关联。
在基线基因型中发现了一些继发性和额外的突变。在治疗期间，当病毒未得到最佳抑制时，会出现耐药突变，这些突变取决于亚型和拉替拉韦治疗时间。
