欧洲HIV耐药性的传播及其对当前一线治疗方案的预测影响。
Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe.
作者信息
Hofstra L Marije, Sauvageot Nicolas, Albert Jan, Alexiev Ivailo, Garcia Federico, Struck Daniel, Van de Vijver David A M C, Åsjö Birgitta, Beshkov Danail, Coughlan Suzie, Descamps Diane, Griskevicius Algirdas, Hamouda Osamah, Horban Andrzej, Van Kasteren Marjo, Kolupajeva Tatjana, Kostrikis Leondios G, Liitsola Kirsi, Linka Marek, Mor Orna, Nielsen Claus, Otelea Dan, Paraskevis Dimitrios, Paredes Roger, Poljak Mario, Puchhammer-Stöckl Elisabeth, Sönnerborg Anders, Staneková Danica, Stanojevic Maja, Van Laethem Kristel, Zazzi Maurizio, Zidovec Lepej Snjezana, Boucher Charles A B, Schmit Jean-Claude, Wensing Annemarie M J, Puchhammer-Stockl E, Sarcletti M, Schmied B, Geit M, Balluch G, Vandamme A-M, Vercauteren J, Derdelinckx I, Sasse A, Bogaert M, Ceunen H, De Roo A, De Wit S, Echahidi F, Fransen K, Goffard J-C, Goubau P, Goudeseune E, Yombi J-C, Lacor P, Liesnard C, Moutschen M, Pierard D, Rens R, Schrooten Y, Vaira D, Vandekerckhove L P R, Van den Heuvel A, Van Der Gucht B, Van Ranst M, Van Wijngaerden E, Vandercam B, Vekemans M, Verhofstede C, Clumeck N, Van Laethem K, Beshkov D, Alexiev I, Lepej S Zidovec, Begovac J, Kostrikis L, Demetriades I, Kousiappa I, Demetriou V, Hezka J, Linka M, Maly M, Machala L, Nielsen C, Jørgensen L B, Gerstoft J, Mathiesen L, Pedersen C, Nielsen H, Laursen A, Kvinesdal B, Liitsola K, Ristola M, Suni J, Sutinen J, Descamps D, Assoumou L, Castor G, Grude M, Flandre P, Storto A, Hamouda O, Kücherer C, Berg T, Braun P, Poggensee G, Däumer M, Eberle J, Heiken H, Kaiser R, Knechten H, Korn K, Müller H, Neifer S, Schmidt B, Walter H, Gunsenheimer-Bartmeyer B, Harrer T, Paraskevis D, Hatzakis A, Zavitsanou A, Vassilakis A, Lazanas M, Chini M, Lioni A, Sakka V, Kourkounti S, Paparizos V, Antoniadou A, Papadopoulos A, Poulakou G, Katsarolis I, Protopapas K, Chryssos G, Drimis S, Gargalianos P, Xylomenos G, Lourida G, Psichogiou M, Daikos G L, Sipsas N V, Kontos A, Gamaletsou M N, Koratzanis G, Sambatakou H, Mariolis H, Skoutelis A, Papastamopoulos V, Georgiou O, Panagopoulos P, Maltezos E, Coughlan S, De Gascun C, Byrne C, Duffy M, Bergin C, Reidy D, Farrell G, Lambert J, O'Connor E, Rochford A, Low J, Coakely P, O'Dea S, Hall W, Mor O, Levi I, Chemtob D, Grossman Z, Zazzi M, de Luca A, Balotta C, Riva C, Mussini C, Caramma I, Capetti A, Colombo M C, Rossi C, Prati F, Tramuto F, Vitale F, Ciccozzi M, Angarano G, Rezza G, Kolupajeva T, Vasins O, Griskevicius A, Lipnickiene V, Schmit J C, Struck D, Sauvageot N, Hemmer R, Arendt V, Michaux C, Staub T, Sequin-Devaux C, Wensing A M J, Boucher C A B, van de Vijver D A M C, van Kessel A, van Bentum P H M, Brinkman K, Connell B J, van der Ende M E, Hoepelman I M, van Kasteren M, Kuipers M, Langebeek N, Richter C, Santegoets R M W J, Schrijnders-Gudde L, Schuurman R, van de Ven B J M, Åsjö B, Kran A-M Bakken, Ormaasen V, Aavitsland P, Horban A, Stanczak J J, Stanczak G P, Firlag-Burkacka E, Wiercinska-Drapalo A, Jablonowska E, Maolepsza E, Leszczyszyn-Pynka M, Szata W, Camacho R, Palma C, Borges F, Paixão T, Duque V, Araújo F, Otelea D, Paraschiv S, Tudor A M, Cernat R, Chiriac C, Dumitrescu F, Prisecariu L J, Stanojevic M, Jevtovic Dj, Salemovic D, Stanekova D, Habekova M, Chabadová Z, Drobkova T, Bukovinova P, Shunnar A, Truska P, Poljak M, Lunar M, Babic D, Tomazic J, Vidmar L, Vovko T, Karner P, Garcia F, Paredes R, Monge S, Moreno S, Del Amo J, Asensi V, Sirvent J L, de Mendoza C, Delgado R, Gutiérrez F, Berenguer J, Garcia-Bujalance S, Stella N, de Los Santos I, Blanco J R, Dalmau D, Rivero M, Segura F, Elías M J Pérez, Alvarez M, Chueca N, Rodríguez-Martín C, Vidal C, Palomares J C, Viciana I, Viciana P, Cordoba J, Aguilera A, Domingo P, Galindo M J, Miralles C, Del Pozo M A, Ribera E, Iribarren J A, Ruiz L, de la Torre J, Vidal F, Clotet B, Albert J, Heidarian A, Aperia-Peipke K, Axelsson M, Mild M, Karlsson A, Sönnerborg A, Thalme A, Navér L, Bratt G, Karlsson A, Blaxhult A, Gisslén M, Svennerholm B, Bergbrant I, Björkman P, Säll C, Mellgren Å, Lindholm A, Kuylenstierna N, Montelius R, Azimi F, Johansson B, Carlsson M, Johansson E, Ljungberg B, Ekvall H, Strand A, Mäkitalo S, Öberg S, Holmblad P, Höfer M, Holmberg H, Josefson P, Ryding U
机构信息
Luxembourg Institute of Health, Luxembourg.
Department of Virology, University Medical Center Utrecht, The Netherlands.
出版信息
Clin Infect Dis. 2016 Mar 1;62(5):655-663. doi: 10.1093/cid/civ963. Epub 2015 Nov 29.
BACKGROUND
Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001.
METHODS
Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0.
RESULTS
The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones.
CONCLUSIONS
Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.
背景
众多研究表明，基线耐药模式可能会影响抗逆转录病毒治疗的结果。因此，指南推荐进行耐药性检测以指导初始治疗方案的选择。除了优化个体患者管理外，这些基线耐药数据还可用于公共卫生目的的传播性耐药（TDR）调查。SPREAD项目自2001年起系统收集数据，以深入了解欧洲发生的TDR情况。
方法
对2008年至2010年间新诊断的来自26个国家的4140例未接受过抗逆转录病毒治疗的人类免疫缺陷病毒（HIV）感染个体的人口统计学、临床和病毒学数据进行分析。使用世界卫生组织耐药突变监测清单定义TDR证据。通过将结果与2002年至2007年的SPREAD数据进行比较，评估TDR随时间的流行情况。使用斯坦福HIVdb程序7.0版预测对抗逆转录病毒药物的基线敏感性。
结果
TDR的总体流行率随时间没有显著变化，在2008 - 2010年为8.3%（95%置信区间，7.2% - 9.5%）。TDR最常见的指标是核苷类逆转录酶抑制剂（NRTI）突变（4.5%），其次是非核苷类逆转录酶抑制剂（NNRTI）突变（2.9%）和蛋白酶抑制剂突变（2.0%）。基线突变对基于初始NNRTI方案的敏感性降低最具预测性：分别有4.5%和6.5%的患者分离株预计对含依非韦伦或利匹韦林的方案耐药，与当前的NRTI主干无关。
结论
虽然NRTI的TDR最高，但基线耐药模式对敏感性的影响在NNRTI方面最大。通过流行病学调查评估的TDR流行率并未明确表明不同药物类别敏感性受影响的程度。
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