Perez E E, Rose S L, Peyser B, Lamers S L, Burkhardt B, Dunn B M, Hutson A D, Sleasman J W, Goodenow M M
Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
J Infect Dis. 2001 Feb 15;183(4):579-88. doi: 10.1086/318538. Epub 2001 Jan 19.
Protease genotype, as a variable in outcome to combination therapy for human immunodeficiency virus (HIV) type 1 infection, was evaluated among protease inhibitor-naive children and adolescents who had received extensive treatment with reverse-transcriptase inhibitors. After 24 weeks of combination therapy, 35% had viral and immune success (VSIS patients), 19% had viral and immune failure (VFIF patients), and 46% had viral failure but marked improvement in CD4 T cells (VFIS patients). Disease stage was the only pretherapy clinical variable associated with outcome (P=.02). Although reverse-transcriptase genotype was unrelated to outcome, pretherapy protease genotype was related significantly to therapy response (P=.005). Odds for immune or viral failure were 17.7 to 1 and 2.5 to 1, respectively, for protease genotype as a single variable. Protease genotype combined with disease stage and CD4 cell percentage predicted correct therapy response for 81% of patients (100% of VFIF, 78% of VSIS, and 75% of VFIS patiens). Naturally occurring amino acid polymorphisms in protease provide sensitive biomarkers for treatment response among inhibitor-naive patients with advanced HIV disease.
在未曾接受过蛋白酶抑制剂治疗、但已接受过大量逆转录酶抑制剂治疗的儿童和青少年中，对蛋白酶基因型作为人类免疫缺陷病毒1型（HIV-1）感染联合治疗结果的一个变量进行了评估。联合治疗24周后，35%的患者获得病毒学和免疫学成功（VSIS患者），19%的患者出现病毒学和免疫学失败（VFIF患者），46%的患者出现病毒学失败，但CD4 T细胞有显著改善（VFIS患者）。疾病阶段是唯一与治疗结果相关的治疗前临床变量（P = 0.02）。虽然逆转录酶基因型与治疗结果无关，但治疗前蛋白酶基因型与治疗反应显著相关（P = 0.005）。作为单一变量，蛋白酶基因型出现免疫或病毒学失败的几率分别为17.7比1和2.5比1。蛋白酶基因型与疾病阶段和CD4细胞百分比相结合，可预测81%患者的正确治疗反应（VFIF患者为100%，VSIS患者为78%，VFIS患者为75%）。蛋白酶中自然发生的氨基酸多态性为晚期HIV疾病初治患者的治疗反应提供了敏感的生物标志物。
