传播耐药性对初始联合抗逆转录病毒治疗 HIV 的病毒学和免疫学反应的影响（EuroCoord-CHAIN 联合项目）：一项欧洲多队列研究。

Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study.

机构信息

INSERM U897 Centre of Epidemiology and Biostatistics, ISPED Bordeaux School of Public Health, University Bordeaux Segalen, Bordeaux, France.

出版信息

Lancet Infect Dis. 2011 May;11(5):363-71. doi: 10.1016/S1473-3099(11)70032-9. Epub 2011 Feb 25.

DOI:10.1016/S1473-3099(11)70032-9

PMID:21354861

Abstract

BACKGROUND

The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration.

METHODS

HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy.

FINDINGS

Of 10,056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093).

INTERPRETATION

These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients.

FUNDING

European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.

摘要

背景

传播性耐药（TDR）对 HIV-1 的一线联合抗逆转录病毒治疗（cART）的影响需要进一步研究，以为最佳药物方案的选择提供信息。我们在一个大型的欧洲合作研究中调查了 TDR 对 cART 第一年结果的影响。

方法

本研究纳入了年龄不限的 HIV 感染者，如果他们在 1998 年 1 月 1 日之后首次开始 cART（至少三种抗逆转录病毒药物），并且在开始 cART 前至少有一个用于基因分型检测的样本，并且对任何一种抗逆转录病毒药物均无耐药性。我们使用世界卫生组织（WHO）的耐药性列表和斯坦福算法将患者分为三种耐药类别：无 TDR、至少一种突变和完全有效的 cART，或至少一种突变和至少一种处方药物耐药。病毒学失败定义为在治疗 6 个月后，两次连续病毒载量测量中，有两次连续的病毒载量测量值超过 500 拷贝/ml。

结果

在来自 25 个队列的 10056 名患者中，9102 名（90.5%）患者 HIV 无 TDR，475 名（4.7%）患者至少有一种突变，但接受了完全有效的 cART，479 名（4.8%）患者至少有一种突变且对至少一种药物耐药。在 12 个月时，无 TDR 组、TDR 和完全有效的 cART 组和 TDR 和耐药组的病毒学失败累积 Kaplan-Meier 估计值分别为 4.2%（95%CI 3.8-4.7）、4.7%（2.9-7.5）和 15.1%（11.9-19.0）（对数秩检验 p<0.0001）。TDR 和至少一种药物耐药与无 TDR 患者之间病毒学失败差异的风险比为 3.13（95%CI 2.33-4.20，p<0.0001）。TDR 接受完全有效的 cART 与无 TDR 患者之间病毒学失败差异的风险比为 1.47（95%CI 0.19-2.38，p=0.12）。在分层分析中，TDR 接受包含非核苷类逆转录酶抑制剂（NNRTI）的完全有效的 cART 与无 TDR 患者相比，病毒学失败的风险比为 2.0（95%CI 0.9-4.7，p=0.093）。