Yerly Sabine, Junier Thomas, Gayet-Ageron Angèle, Amari Emmanuelle Boffi El, von Wyl Viktor, Günthard Huldrych F, Hirschel Bernard, Zdobnov Evgeny, Kaiser Laurent
University of Geneva Medical School, Geneva's University Hospitals, Switzerland.
AIDS. 2009 Jul 17;23(11):1415-23. doi: 10.1097/QAD.0b013e32832d40ad.
To monitor HIV-1 transmitted drug resistance (TDR) in a well defined urban area with large access to antiretroviral therapy and to assess the potential source of infection of newly diagnosed HIV individuals.
All individuals resident in Geneva, Switzerland, with a newly diagnosed HIV infection between 2000 and 2008 were screened for HIV resistance. An infection was considered as recent when the positive test followed a negative screening test within less than 1 year. Phylogenetic analyses were performed by using the maximum likelihood method on pol sequences including 1058 individuals with chronic infection living in Geneva.
Of 637 individuals with newly diagnosed HIV infection, 20% had a recent infection. Mutations associated with resistance to at least one drug class were detected in 8.5% [nucleoside reverse transcriptase inhibitors (NRTIs), 6.3%; non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3.5%; protease inhibitors, 1.9%]. TDR (P-trend = 0.015) and, in particular, NNRTI resistance (P = 0.002) increased from 2000 to 2008. Phylogenetic analyses revealed that 34.9% of newly diagnosed individuals, and 52.7% of those with recent infection were linked to transmission clusters. Clusters were more frequent in individuals with TDR than in those with sensitive strains (59.3 vs. 32.6%, respectively; P < 0.0001). Moreover, 84% of newly diagnosed individuals with TDR were part of clusters composed of only newly diagnosed individuals.
Reconstruction of the HIV transmission networks using phylogenetic analysis shows that newly diagnosed HIV infections are a significant source of onward transmission, particularly of resistant strains, thus suggesting an important self-fueling mechanism for TDR.
在一个有大量机会接受抗逆转录病毒治疗的特定城区监测HIV-1传播耐药性（TDR），并评估新诊断HIV感染者的潜在感染源。
对2000年至2008年间瑞士日内瓦所有新诊断为HIV感染的居民进行HIV耐药性筛查。当阳性检测结果在不到1年的时间内出现在阴性筛查检测之后时，该感染被视为近期感染。使用最大似然法对包括1058名居住在日内瓦的慢性感染个体的pol序列进行系统发育分析。
在637名新诊断为HIV感染的个体中，20%有近期感染。在8.5%的个体中检测到与至少一种药物类别耐药相关的突变[核苷类逆转录酶抑制剂（NRTIs），6.3%；非核苷类逆转录酶抑制剂（NNRTIs），3.5%；蛋白酶抑制剂，1.9%]。从2000年到2008年，TDR（P趋势=0.015），尤其是NNRTI耐药性（P=0.002）有所增加。系统发育分析显示，34.9%的新诊断个体和52.7%的近期感染个体与传播簇相关。与敏感毒株个体相比，TDR个体中的簇更常见（分别为59.3%和32.6%；P<0.0001）。此外，84%的新诊断为TDR的个体是仅由新诊断个体组成的簇的一部分。
使用系统发育分析重建HIV传播网络表明，新诊断的HIV感染是后续传播的重要来源，尤其是耐药毒株的传播，因此提示了TDR的一种重要的自我促进机制。
