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来自外周血和淋巴结的人类免疫缺陷病毒前病毒DNA显示出对齐多夫定(密码子215)和去羟肌苷(密码子74)的一致耐药突变。艾滋病治疗研究倡议003研究组。

Human immunodeficiency virus proviral DNA from peripheral blood and lymph nodes demonstrates concordant resistance mutations to zidovudine (codon 215) and didanosine (codon 74). Division of AIDS Treatment Research Initiative 003 Study Group.

作者信息

Mayers D, Bethel J, Wainberg M A, Weislow O, Schnittman S

机构信息

Naval Medical Research Institute and Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

J Infect Dis. 1998 Jun;177(6):1730-3. doi: 10.1086/517433.

Abstract

Genotypes that confer drug resistance were evaluated in human immunodeficiency virus (HIV) proviral DNA obtained from peripheral blood mononuclear cells (PBMC) and lymphoid tissue at baseline and after 8 weeks of therapy with zidovudine alone or in combination with didanosine from 22 patients (8 zidovudine-naive and 14 zidovudine-experienced). There was evidence of zidovudine resistance at codon 215 in 27.3% (6/22) of patients. All 20 patients evaluable for codon 74 (site of didanosine resistance) had virus that remained wild type during the 8-week study period. When HIV proviral DNA from PBMC was compared with that from lymphoid tissue, 94.7% (18/19) of evaluable samples were concordant at codon 215 at baseline, while 85.7% (12/14) were concordant at week 8. Resistance in PBMC (but not in lymphoid tissue) developed in 1 of 8 zidovudine-naive patients; an increased proportion of resistant strains in PBMC (but not in lymphoid tissue) was observed in 2 of 14 zidovudine-experienced patients. These results suggest high concordance for drug resistance mutations in HIV proviral DNA from blood and lymph node tissue.

摘要

在22例患者(8例初治齐多夫定患者和14例接受过齐多夫定治疗的患者)中,对从外周血单核细胞(PBMC)和淋巴组织获取的人类免疫缺陷病毒(HIV)前病毒DNA进行评估,以确定赋予耐药性的基因型。这些患者单独使用齐多夫定或联合使用去羟肌苷进行了8周治疗,治疗前和治疗8周后分别进行评估。有证据表明,27.3%(6/22)的患者在215密码子处出现齐多夫定耐药。在对74密码子(去羟肌苷耐药位点)进行评估的所有20例患者中,在为期8周的研究期间,病毒均保持野生型。当将PBMC中的HIV前病毒DNA与淋巴组织中的进行比较时,在基线时,94.7%(18/19)可评估样本在215密码子处一致,而在第8周时,85.7%(12/14)一致。8例初治齐多夫定患者中有1例在PBMC中出现耐药(但淋巴组织中未出现);14例接受过齐多夫定治疗的患者中有2例在PBMC中观察到耐药毒株比例增加(但淋巴组织中未出现)。这些结果表明,血液和淋巴结组织中HIV前病毒DNA的耐药突变具有高度一致性。

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