De Antoni A, Foli A, Lisziewicz J, Lori F
Research Institute for Genetic and Human Therapy, Washington, DC, USA.
J Infect Dis. 1997 Oct;176(4):899-903. doi: 10.1086/516511.
The pattern of mutations in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) strains that confer resistance to didanosine (ddI) was analyzed in 2 groups of patients receiving either ddI monotherapy or ddI plus hydroxyurea (HU) combination therapy. Twelve patients receiving combination therapy and 8 receiving monotherapy were tested. Combinations of ddI plus HU did not prevent the onset of mutations, which emerged in 50% of the patients in this group compared with 25% of the ddI monotherapy group. In addition, in 1 patient from the combination therapy arm, who had a limited response to the therapy, an unusual pattern of mutations was found: the insertion of 2 amino acids between residues 69 and 70, a region critical for resistance to nucleoside analogs. The higher efficacy of the combination of HU and ddI compared with that of ddI monotherapy cannot be attributed to a delayed or decreased onset of resistance to ddI.
在两组接受去羟肌苷（ddI）单药治疗或ddI加羟基脲（HU）联合治疗的患者中，分析了对ddI产生耐药性的1型人类免疫缺陷病毒（HIV-1）毒株逆转录酶（RT）中的突变模式。对12名接受联合治疗的患者和8名接受单药治疗的患者进行了检测。ddI加HU的联合用药并不能预防突变的出现，该组中50%的患者出现了突变，而ddI单药治疗组这一比例为25%。此外，在联合治疗组中有1名对治疗反应有限的患者，发现了一种不寻常的突变模式：在第69和70位氨基酸残基之间插入了2个氨基酸，该区域对核苷类似物耐药性至关重要。HU与ddI联合用药的疗效高于ddI单药治疗，这不能归因于对ddI耐药性的延迟出现或降低。
