广泛开展抗逆转录病毒治疗十年后洪都拉斯的艾滋病毒耐药性监测
HIV Drug Resistance Surveillance in Honduras after a Decade of Widespread Antiretroviral Therapy.
作者信息
Avila-Ríos Santiago, García-Morales Claudia, Tapia-Trejo Daniela, Meza Rita I, Nuñez Sandra M, Parham Leda, Flores Norma A, Valladares Diana, Pineda Luisa M, Flores Dixiana, Motiño Roxana, Umanzor Víctor, Carbajal Candy, Murillo Wendy, Lorenzana Ivette, Palou Elsa Y, Reyes-Terán Gustavo
机构信息
Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.
HIV National Programme and National Laboratory, Honduran Ministry of Health, Tegucigalpa, Honduras.
出版信息
PLoS One. 2015 Nov 11;10(11):e0142604. doi: 10.1371/journal.pone.0142604. eCollection 2015.
INTRODUCTION
We assessed HIV drug resistance (DR) in individuals failing ART (acquired DR, ADR) and in ART-naïve individuals (pre-ART DR, PDR) in Honduras, after 10 years of widespread availability of ART.
METHODS
365 HIV-infected, ART-naïve, and 381 ART-experienced Honduran individuals were enrolled in 5 reference centres in Tegucigalpa, San Pedro Sula, La Ceiba, and Choluteca between April 2013 and April 2015. Plasma HIV protease-RT sequences were obtained. HIVDR was assessed using the WHO HIVDR mutation list and the Stanford algorithm. Recently infected (RI) individuals were identified using a multi-assay algorithm.
RESULTS
PDR to any ARV drug was 11.5% (95% CI 8.4-15.2%). NNRTI PDR prevalence (8.2%) was higher than NRTI (2.2%) and PI (1.9%, p<0.0001). No significant trends in time were observed when comparing 2013 and 2014, when using a moving average approach along the study period or when comparing individuals with >500 vs. <350 CD4+ T cells/μL. PDR in recently infected individuals was 13.6%, showing no significant difference with PDR in individuals with longstanding infection (10.7%). The most prevalent PDR mutations were M46IL (1.4%), T215 revertants (0.5%), and K103NS (5.5%). The overall ADR prevalence in individuals with <48 months on ART was 87.8% and for the ≥48 months on ART group 81.3%. ADR to three drug families increased in individuals with longer time on ART (p = 0.0343). M184V and K103N were the most frequent ADR mutations. PDR mutation frequency correlated with ADR mutation frequency for PI and NNRTI (p<0.01), but not for NRTI. Clusters of viruses were observed suggesting transmission of HIVDR both from ART-experienced to ART-naïve individuals and between ART-naïve individuals.
CONCLUSIONS
The global PDR prevalence in Honduras remains at the intermediate level, after 10 years of widespread availability of ART. Evidence of ADR influencing the presence of PDR was observed by phylogenetic analyses and ADR/PDR mutation frequency correlations.
引言
在抗逆转录病毒疗法（ART）广泛应用10年后，我们评估了洪都拉斯接受ART治疗失败的个体（获得性耐药，ADR）和未接受过ART治疗的个体（ART治疗前耐药，PDR）中的HIV耐药情况。
方法
2013年4月至2015年4月期间，在特古西加尔巴、圣佩德罗苏拉、拉塞瓦和乔卢特卡的5个参考中心招募了365名未接受过ART治疗的HIV感染者和381名有ART治疗经验的洪都拉斯个体。获取血浆HIV蛋白酶-RT序列。使用世界卫生组织HIV耐药突变列表和斯坦福算法评估HIV耐药情况。使用多检测算法识别近期感染（RI）个体。
结果
对任何抗逆转录病毒药物的PDR为11.5%（95%CI 8.4 - 15.2%）。非核苷类逆转录酶抑制剂（NNRTI）的PDR患病率（8.2%）高于核苷类逆转录酶抑制剂（NRTI，2.2%）和蛋白酶抑制剂（PI，1.9%，p<0.0001）。在比较2013年和2014年、沿研究期使用移动平均法或比较CD4+T细胞/μL>500与<350的个体时，未观察到明显的时间趋势。近期感染个体的PDR为13.6%，与长期感染个体的PDR（10.7%）无显著差异。最常见的PDR突变是M46IL（1.4%）、T215回复突变（0.5%）和K103NS（5.5%）。接受ART治疗<48个月的个体中ADR总体患病率为87.8%，接受ART治疗≥48个月的个体组为81.3%。接受ART治疗时间较长的个体对三类药物的ADR增加（p = 0.0343）。M184V和K103N是最常见的ADR突变。PI和NNRTI的PDR突变频率与ADR突变频率相关（p<0.01），但NRTI不相关。观察到病毒簇，表明HIV耐药可从有ART治疗经验的个体传播到未接受过ART治疗的个体，也可在未接受过ART治疗的个体之间传播。
结论
在ART广泛应用10年后，洪都拉斯的全球PDR患病率仍处于中等水平。通过系统发育分析和ADR/PDR突变频率相关性观察到ADR影响PDR存在的证据。
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