Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
PLoS One. 2012;7(3):e33484. doi: 10.1371/journal.pone.0033484. Epub 2012 Mar 20.
Transmitted drug resistance (TDR) is a clinical and epidemiological problem because it may contribute to failure of antiretroviral treatment. The prevalence of TDR varies geographically, and its prevalence in Sweden during the last decade has not been reported. Plasma samples from 1,463 patients newly diagnosed with HIV-1 infection between 2003 and 2010, representing 44% of all patients diagnosed in Sweden during this period, were analyzed using the WHO 2009 list of mutations for surveillance of TDR. Maximum likelihood phylogenetic analyses were used to determine genetic subtype and to investigate the relatedness of the sequences. Eighty-two patients showed evidence of TDR, representing a prevalence of 5.6% (95% CI: 4.5%-6.9%) without any significant time trends or differences between patients infected in Sweden or abroad. Multivariable logistic regression showed that TDR was positively associated with men who have sex with men (MSM) and subtype B infection and negatively associated with CD4 cell counts. Among patients with TDR, 54 (68%) had single resistance mutations, whereas five patients had multi-drug resistant HIV-1. Phylogenetic analyses identified nine significantly supported clusters involving 29 of the patients with TDR, including 23 of 42 (55%) of the patients with TDR acquired in Sweden. One cluster contained 18 viruses with a M41L resistance mutation, which had spread among MSM in Stockholm over a period of at least 16 years (1994-2010). Another cluster, which contained the five multidrug resistant viruses, also involved MSM from Stockholm. The prevalence of TDR in Sweden 2003-2010 was lower than in many other European countries. TDR was concentrated among MSM, where clustering of TDR strains was observed, which highlights the need for continued and improved measures for targeted interventions.
传播性耐药(TDR)是一个临床和流行病学问题,因为它可能导致抗逆转录病毒治疗失败。TDR 的流行情况因地理位置而异,而瑞典在过去十年中的 TDR 流行情况尚未有报道。分析了 2003 年至 2010 年间新诊断为 HIV-1 感染的 1463 名患者的血浆样本,这些患者代表了瑞典同期所有确诊患者的 44%,这些样本使用世界卫生组织(WHO)2009 年的耐药监测突变列表进行了分析。最大似然系统发育分析用于确定遗传亚型并研究序列之间的相关性。82 名患者显示出 TDR 的证据,其流行率为 5.6%(95%CI:4.5%-6.9%),没有明显的时间趋势或在瑞典或国外感染的患者之间存在差异。多变量逻辑回归显示,TDR 与男男性行为者(MSM)和 B 型感染呈正相关,与 CD4 细胞计数呈负相关。在 TDR 患者中,54 名(68%)患者有单耐药突变,而 5 名患者有耐多药 HIV-1。系统发育分析确定了 9 个具有显著支持力的聚类,涉及 29 名 TDR 患者,包括 42 名(55%)在瑞典获得 TDR 的患者。一个聚类包含 18 种具有 M41L 耐药突变的病毒,这些病毒在斯德哥尔摩的 MSM 中传播了至少 16 年(1994-2010 年)。另一个聚类,其中包含 5 种耐多药病毒,也涉及来自斯德哥尔摩的 MSM。2003-2010 年瑞典的 TDR 流行率低于许多其他欧洲国家。TDR 集中在 MSM 中,观察到 TDR 株的聚类,这突出了需要持续和改进有针对性干预措施的必要性。