Collier A C, Coombs R W, Fischl M A, Skolnik P R, Northfelt D, Boutin P, Hooper C J, Kaplan L D, Volberding P A, Davis L G, Henrard D R, Weller S, Corey L
University of Washington School of Medicine, Seattle.
Ann Intern Med. 1993 Oct 15;119(8):786-93. doi: 10.7326/0003-4819-119-8-199310150-00003.
To assess safety, pharmacokinetics, and in-vivo virologic activity of five different combination regimens of zidovudine and didanosine compared with zidovudine alone in patients with human immunodeficiency virus type 1 (HIV-1) infection.
Open-label, partially randomized, dose-ranging study.
University-affiliated, medical center clinics.
A total of 69 patients with HIV-1 infection, CD4+ cell counts fewer than 400 cells/mm3, and fewer than 121 days of previous zidovudine treatment.
Fifty-five patients received combination therapy with zidovudine and didanosine, and 14 received zidovudine therapy alone (600 mg/d). Daily dosages in milligrams of zidovudine and didanosine, respectively, in the five combination groups were 150 and 90 mg, 300 and 334 mg, 600 and 334 mg, 300 and 500 mg, and 600 and 500 mg.
CD4+ cell counts, HIV-1 RNA titers in plasma, and toxic effects.
The combination regimens were associated with higher and more sustained increases in CD4+ cells than zidovudine alone, even after adjustment for initial CD4+ counts and previous zidovudine therapy (P < 0.001). The median increase in CD4+ cell counts was 166 cells/mm3 with combination therapy and 77 cells/mm3 with zidovudine alone (P = 0.001) and did not differ statistically among the five combination regimens. Human immunodeficiency virus type 1 RNA titers in plasma decreased in 15 (83%) of 18 combination-therapy recipients compared with 2 of 7 zidovudine-alone recipients (P = 0.017). No pharmacokinetic interactions were seen between zidovudine and didanosine. Toxicity rates were low among all treatment groups. A greater decrease in hemoglobin levels was seen with the regimen using zidovudine alone (-8 g/L) compared with combination regimens using the same zidovudine dose (-1.5 g/L, P = 0.03).
Combination therapy with zidovudine and didanosine produced larger and more sustained increases in CD4+ cell counts, more frequent decreases in plasma HIV-1 RNA titers, and more stable hematologic status than zidovudine therapy alone. The effects of this combination on the progression of HIV disease merit further study, to provide information about clinical outcome, because this was a relatively small study based on surrogate markers of HIV-1 infection.
评估齐多夫定与去羟肌苷的五种不同联合治疗方案相较于单独使用齐多夫定治疗人类免疫缺陷病毒1型（HIV-1）感染患者的安全性、药代动力学及体内病毒学活性。
开放标签、部分随机、剂量范围研究。
大学附属医院医疗中心诊所。
共有69例HIV-1感染患者，CD4+细胞计数少于400个细胞/mm³，且之前接受齐多夫定治疗少于121天。
55例患者接受齐多夫定与去羟肌苷联合治疗，14例患者仅接受齐多夫定治疗（600mg/d）。五个联合治疗组中齐多夫定和去羟肌苷的每日剂量分别为150mg和90mg、300mg和334mg、600mg和334mg、300mg和500mg、600mg和500mg。
CD4+细胞计数、血浆中HIV-1 RNA滴度及毒性作用。
即使在对初始CD4+计数和之前的齐多夫定治疗进行调整后，联合治疗方案相较于单独使用齐多夫定能使CD4+细胞有更高且更持久的增加（P<0.001）。联合治疗组CD4+细胞计数的中位数增加为166个细胞/mm³，单独使用齐多夫定组为77个细胞/mm³（P = 0.001），且五个联合治疗方案之间无统计学差异。18例接受联合治疗的患者中有15例（83%）血浆中HIV-1 RNA滴度下降，而7例单独使用齐多夫定的患者中仅有2例下降（P = 0.017）。未观察到齐多夫定与去羟肌苷之间存在药代动力学相互作用。所有治疗组的毒性发生率均较低。与使用相同齐多夫定剂量的联合治疗方案（-1.5g/L，P = 0.03）相比，单独使用齐多夫定的方案使血红蛋白水平下降幅度更大（-8g/L）。
与单独使用齐多夫定治疗相比，齐多夫定与去羟肌苷联合治疗能使CD4+细胞计数有更大且更持久的增加，血浆HIV-1 RNA滴度更频繁下降，血液学状态更稳定。由于这是一项基于HIV-1感染替代指标的相对小型研究，该联合治疗对HIV疾病进展的影响值得进一步研究以提供有关临床结局的信息。
