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当前抗逆转录病毒治疗方案对中国艾滋病患者的影响及其对HIV-1耐药性突变的意义。

The impacts of current antiretroviral therapy regimens on Chinese AIDS patients and their implications for HIV-1 drug resistance mutation.

作者信息

Zhang Min, Han Xiao-Xu, Cui Wei-Guo, Jia Man-Hong, Meng Xiang-Dong, Xing Ai-Hua, Wu Yu-Hua, Yang Ying-Yuan, Lu Chun-Ming, Hu Qing-Hai, Dai Di, Zhang Zi-Ning, Shang Hong

机构信息

Key Laboratory of Immunology of AIDS, Ministry of Health, The First Hospital, China Medical University, Shenyang, P. R. China.

出版信息

Jpn J Infect Dis. 2008 Sep;61(5):361-5.

PMID:18806342
Abstract

This study sought to investigate the impacts of the antiretroviral (ARV) therapy regimens currently used in Chinese HIV-1-infected individuals. Seven hundred eighteen ARV-treated and treatment-naive HIV-1-infected individuals living in seven provinces were enrolled in 2005 by a multistage sampling approach according to a national cross-sectional survey program on HIV-1 drug resistance. All patients were investigated clinically, and CD4+ T cell counts and HIV-1 viral loads were measured while genotyping for drug resistance was determined by a home brew nested PCR. Viral inhibition in ARV-treated individuals was higher than that in ARV treatment-naive individuals. The overall prevalence of drug-resistant mutations was 37.8%. Higher frequencies of mutations in ARV-treated and drug withdrawal groups were found than in the ARV treatment-naive group (P<0.01). Of the four regimens currently used, the D4T/3TC/NVP regimen showed a higher-level viral inhibition. No statistical significance was found among the four regimens in drug-resistant mutations. The rate of resistance-associated mutations to non-nucleotide reverse transcriptase inhibitors (NNRTIs) was higher than that to nucleotide reverse transcriptase inhibitors (NRTIs) (P<0.01). The most common mutations conferring resistance to NNRTIs were K103N, Y181C and G190A, representing 56.5, 30.4 and 14.5%, respectively. Furthermore, higher viral inhibition and a lower rate of drug-resistant mutations were achieved in the good compliance group. This study revealed an efficient viral inhibition achieved with the current first-line regimens in China. Most of these regimens could rapidly result in emergence of drug-resistant mutations, suggesting that a second-line ARV therapy is urgently needed and that the compliance with treatment must be emphasized during long-term treatment.

摘要

本研究旨在调查目前在中国感染HIV-1的个体中使用的抗逆转录病毒(ARV)治疗方案的影响。根据一项关于HIV-1耐药性的全国横断面调查计划,2005年采用多阶段抽样方法,招募了居住在7个省份的718名接受ARV治疗和未接受过治疗的HIV-1感染个体。对所有患者进行临床检查,测量CD4+T细胞计数和HIV-1病毒载量,同时通过自制巢式PCR确定耐药基因分型。接受ARV治疗的个体的病毒抑制率高于未接受ARV治疗的个体。耐药突变的总体发生率为37.8%。与未接受ARV治疗的组相比,接受ARV治疗和停药组的突变频率更高(P<0.01)。在目前使用的四种治疗方案中,D4T/3TC/NVP方案显示出较高水平的病毒抑制。四种治疗方案在耐药突变方面未发现统计学差异。对非核苷类逆转录酶抑制剂(NNRTIs)的耐药相关突变率高于对核苷类逆转录酶抑制剂(NRTIs)的耐药相关突变率(P<0.01)。对NNRTIs耐药的最常见突变是K103N、Y181C和G190A,分别占56.5%、30.4%和14.5%。此外,依从性良好的组实现了更高的病毒抑制率和更低的耐药突变率。本研究表明,中国目前的一线治疗方案能有效抑制病毒。这些方案中的大多数可能会迅速导致耐药突变的出现,这表明迫切需要二线ARV治疗,并且在长期治疗期间必须强调治疗依从性。

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