HIV-1 B/B'亚型与基线耐药突变与病毒学失败相关：一项中国多中心队列研究

HIV-1 subtype B/B' and baseline drug resistance mutation are associated with virologic failure: a multicenter cohort study in China.

作者信息

Li Yijia, Gu Lijun, Han Yang, Xie Jing, Wang Huanling, Lv Wei, Song Xiaojing, Li Yanling, Iwamoto Aikichi, Ishida Takaomi, Li Taisheng

机构信息

*Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China; †Research Center for Asian Infectious Diseases, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan; and ‡Japan-China Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

出版信息

J Acquir Immune Defic Syndr. 2015 Mar 1;68(3):289-97. doi: 10.1097/QAI.0000000000000473.

DOI:10.1097/QAI.0000000000000473

PMID:25501612

Abstract

BACKGROUND

Distribution of HIV-1 subtypes, transmitted drug resistance (TDR)/drug resistance mutation (DRM), and their impact on response to combination antiretroviral therapy remain poorly understood in China.

METHODS

We analyzed data from our multicenter cohort study with 444 antiretroviral-naive participants recruited between 2008 and 2010. HIV-1 subtype and tropism were determined by V3 sequencing, and TDR/DRM was determined by Pol sequencing. Virologic and immunologic responses were monitored over 96 weeks of follow-up. The initial combination antiretroviral therapy regimen for all patients was nevirapine + lamivudine + zidovudine or stavudine. Analysis 1 included patients who finished 96 weeks of follow-up (n = 379), and analysis 2 included all 444 patients.

RESULTS

Subtype B/B' was associated with higher prevalence of TDR/DRM to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors. Median time to HIV-1 suppression was 18 weeks in all 3 subtype groups. In Cox proportional models for viral suppression, neither viral tropism nor HIV-1 subtypes had any impact on viral suppression; however, subtypes CRF01_AE and C/CRF07_BC/CRF08_BC were associated with lower risk of virologic failure compared with subtype B/B', with adjusted hazard ratio of 0.11 (P = 0.032) and 0.06 (P = 0.036), respectively in analysis 1, 0.42 (P = 0.047) and 0.22 (P = 0.008), respectively in analysis 2. This association was attenuated by adding DRM profiles to multivariate regression models. Neither subtype nor HIV-1 tropism affected immunologic response.

CONCLUSIONS

HIV-1 subtype tended to be associated with virologic but not immunologic response; this effect could be ascribed to baseline DRM.

摘要

背景

在中国，HIV-1亚型的分布、传播性耐药（TDR）/耐药突变（DRM）及其对联合抗逆转录病毒治疗反应的影响仍知之甚少。

方法

我们分析了多中心队列研究的数据，该研究纳入了2008年至2010年间招募的444名未接受过抗逆转录病毒治疗的参与者。通过V3测序确定HIV-1亚型和嗜性，通过Pol测序确定TDR/DRM。在96周的随访中监测病毒学和免疫学反应。所有患者的初始联合抗逆转录病毒治疗方案为奈韦拉平+拉米夫定+齐多夫定或司他夫定。分析1纳入完成96周随访的患者（n = 379），分析2纳入所有444名患者。

结果

B/B'亚型与核苷类逆转录酶抑制剂和非核苷类逆转录酶抑制剂的TDR/DRM较高患病率相关。所有3个亚型组中HIV-1抑制的中位时间为18周。在病毒抑制的Cox比例模型中，病毒嗜性和HIV-1亚型均对病毒抑制无任何影响；然而，与B/B'亚型相比，CRF01_AE和C/CRF07_BC/CRF08_BC亚型的病毒学失败风险较低，分析1中的调整后风险比分别为0.11（P = 0.032）和0.06（P = 0.036），分析2中分别为0.42（P = 0.047）和0.22（P = 0.008）。通过在多变量回归模型中加入DRM谱，这种关联减弱。亚型和HIV-1嗜性均不影响免疫学反应。