摘要
目的研究我国AIDS患者经国产齐多夫定(AZT)、去羟肌苷(ddI)、奈韦拉平(NVP)联合抗病毒治疗3个月时血浆HIV毒株的耐药突变情况。方法收集124例经国产AZT、ddI、NVP联合抗病毒治疗3个月的AIDS患者的抗凝静脉血,流式细胞仪检测CD4^+ T淋巴细胞计数,RT-PCR扩增HIV pol区蛋白酶基因和部分逆转录酶基因片段,并测序,登录网站分析耐药突变。结果26例(21%)患者出现非核苷类逆转录酶抑制剂(NNRTI)耐药突变。共检测到10个位点发生NNRTI耐药突变:K101E/R、K103N/R、V106A/I、V1 79D、Y181C、Y1 88N、G190A/S、P225A、K238E和Y318F/S。发生率最高的突变位点是K1 03N.为8.1%。11例(8.9%)对台拉韦定(DLV)、依非韦伦(EFV)、NVP均高度耐药;19例(15.3%)对NVP高度耐药;15例(12.1%)对EFV高度耐药;11例(8.9%)对DLV高度耐药。5例(4%)患者出现核苷类逆转录酶抑制剂(NRTI)耐药突变,共检测到L210E、T21 5F/Y和K219Q/T三个位点,发生率分别为0.8%、1.6%和1.6%。3例(2.4%)分别出现G73C、184K、147L蛋白酶主要突变。48例(38.7%)出现蛋白酶次要突变:L63P/S/T/A为38.7%,V77I为36.3%,193L为33.0%,A71V/T/G为8.9%.K20*/Q/R为6.5%,D60E为0.8%。耐药组的CD4^+T淋巴细胞计数低于非耐药组.差异有统计学意义(P<0.05)。结论在抗病毒治疗过程中及时检测基因型耐药对尽早发现耐药变异、避免交叉耐药流行和选择恰当的治疗策略有重要意义。在无蛋白酶抑制剂选择压力下,HIV蛋白酶的主要突变及大量次要突变提示,在抗病毒治疗前行基因型耐药检测有重要意义。
Objective To investigate the development of drug-resistant human immunodeficiency virus(HIV) mutations after 3 months therapy with domestic generic azidothymidine (AZT), didanosine(ddI), nevirapine(NVP). Methods The CD4 counts of 124 patients treated with domestic generic AZT, ddI, NVP for 3 months were tested by flow cytometry and drug resistant mutations were detected by genotypic testing. Results Non-nucleoside reverse transcriptase inhibitors(NNRTI) resistant mutations developed in 26(21%)patients and they were K101E/R, K103N/R, V106A/I, V179D, Y181C, Y188N, G190A/S, P225A, K238E and Y318F/S. The most frequent one was K103N (8.1%). Eleven cases(8. 9%) were highly resistant to delavirdine(DLV), efavirenz(EFV) and NVP while 19 cases(15.3%), 15 cases(12. 1%) and 11 cases(8.9%) were resistant to NVP, EFV and DLV, respectively. Nucleoside reverse transcriptase inhibitors(NRTI) resistant mutations developed in 5 cases(4%), which were L210E, 0.8%, 1.6% and 1. 6% respectively. The major T215F/Y and K219Q/T, with the incidence of protein inhibitor (PI) resistant mutations, G73C, I84K and I47L, developed in 3 cases (2. 4%). The minor PI resistant mutations, L63P/S/T/A (38.7%), V77I (36.3%), I93L(33. 0%), A71V/T/G(8. 9%), K20 */Q/R(6. 5%) and D60E (0.8%), developed in 48 cases(38. 7%). CD4 counts of patients infected with resistant HIV were markedly lower than those of who were not (P 〈 0.05). Conclusions The genotypic resistance testing during therapy is of great importance for early detecting drug resistance, and furthermore, for selecting appropriate therapy strategy and avoiding the spread of cross-resistance. Pre-therapy genotypic resistance testing is also important in view of PI resistant mutations developing without PI existence.
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2007年第2期112-116,共5页
Chinese Journal of Infectious Diseases
基金
北京市科学技术委员会重大项目(D0906003000091)