Mayers D, Bethel J, Wainberg M A, Weislow O, Schnittman S
Naval Medical Research Institute and Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Infect Dis. 1998 Jun;177(6):1730-3. doi: 10.1086/517433.
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.
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。