Staszewski S, Katlama C, Harrer T, Massip P, Yeni P, Cutrell A, Tortell S M, Harrigan R P, Steel H, Lanier R E, Pearce G
Universitatsklinikum, Frankfurt, Germany.
AIDS. 1998 Nov 12;12(16):F197-202. doi: 10.1097/00002030-199816000-00001.
To compare antiretroviral efficacy, safety and tolerance of three dosing regimens of the novel nucleoside reverse transcriptase inhibitor, abacavir (1592U89) over 24 weeks and its efficacy in open-label combination with zidovudine and lamivudine.
Sixty HIV-1-infected antiretroviral therapy naive subjects (entry criteria; CD4+ cell count > or = 100 cells/mm(3), plasma HIV-1 RNA > or = 30 000 copies/ml), randomized into 20 subjects per cohort received 100, 300 or 600 mg abacavir twice daily. Subjects successfully completing 24 weeks' randomized therapy could switch to open label therapy (abacavir, zidovudine, lamivudine at 300, 300 and 150 mg twice daily, respectively) for a further 24 weeks of studly, as could subjects meeting one or more switch criteria.
Subjects were assessed for antiretroviral activity by measuring changes in plasma HIV-1 RNA load and CD4+ cell counts. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses.
At week 4, subjects receiving 300 or 600 mg abacavir twice daily had greater reductions in plasma HIV-1 RNA (median changes -1.55 and -1.61 log10) copies/ml, respectively); differences (P = 0.007 and P < or = 0.001, respectively) than subjects receiving 100 mg abacavir twice daily (median change, -0.63 log10 copies/ml). Differences between the 300 and 600 mg twice daily groups were not clinically or statistically significant. At 24 weeks, analysis showed a median change in plasma HIV-1 RNA of -0.70 and -1.30 log10 copies/ml in the 300 and 600 mg twice daily groups, respectively. During the open label phase in which zidovudine/lamivudine was added to 300 mg abacavir twice daily, a further median reduction in plasma HIV-1 RNA of 1.74 log10 copies/ml was seen. At 48 weeks pooled data from all abacavir-treated subjects showed a sustained reduction in plasma HIV-1 RNA of 2.8 log10) copies/ml; 65% and 43% of subjects had < or = 400 and < or = 50 HIV-1 RNA copies/ml, respectively, and a further median increase of 111 CD4+ cells/mm3 were seen. Abacavir was generally well tolerated with few clinically significant adverse events. Two subjects (3.3%) developed hypersensitivity reactions to abacavir. There were no differences between the groups with regard to serious adverse events.
In terms of antiretroviral therapy naive subjects, treatment with 300 or 600 mg abacavir twice daily was statistically superior to a 100 mg twice daily dose at 4 weeks. Combinations therapy containing abacavir-zidovudine-lamivudine was a highly effective antiretroviral regimen, resulting in substantial reductions in plasma HIV-1 RNA which may be comparable to combinations containing protease inhibitors. Abacavir was generally tolerated.
比较新型核苷类逆转录酶抑制剂阿巴卡韦（1592U89）三种给药方案在24周内的抗逆转录病毒疗效、安全性和耐受性，以及其与齐多夫定和拉米夫定开放标签联合用药的疗效。
60名未接受过抗逆转录病毒治疗的HIV-1感染受试者（入选标准：CD4+细胞计数≥100个细胞/mm³，血浆HIV-1 RNA≥30000拷贝/ml），随机分为3组，每组20名受试者，分别接受每日两次100mg、300mg或600mg阿巴卡韦治疗。成功完成24周随机治疗的受试者，以及符合一项或多项换药标准的受试者，可转为开放标签治疗（阿巴卡韦、齐多夫定、拉米夫定分别为每日两次300mg、300mg和150mg），继续进行24周的研究。
通过测量血浆HIV-1 RNA载量和CD4+细胞计数的变化来评估受试者的抗逆转录病毒活性。基于临床不良事件和实验室分析评估安全性和耐受性。
在第4周时，每日两次接受300mg或600mg阿巴卡韦治疗的受试者血浆HIV-1 RNA下降幅度更大（中位数变化分别为-1.55和-1.61 log10拷贝/ml）；与每日两次接受100mg阿巴卡韦治疗的受试者（中位数变化为-0.63 log10拷贝/ml）相比，差异有统计学意义（P值分别为0.007和P≤0.001）。每日两次300mg和600mg组之间的差异在临床和统计学上均无显著意义。在第24周时，分析显示每日两次300mg和600mg组血浆HIV-1 RNA的中位数变化分别为-0.70和-1.30 log10拷贝/ml。在开放标签阶段，当每日两次300mg阿巴卡韦联合齐多夫定/拉米夫定时，血浆HIV-1 RNA进一步中位数下降1.74 log10拷贝/ml。在第48周时，所有接受阿巴卡韦治疗受试者的汇总数据显示血浆HIV-1 RNA持续下降2.8 log10拷贝/ml；分别有65%和43%的受试者血浆HIV-1 RNA拷贝数≤400和≤50，并且CD4+细胞/mm³中位数进一步增加111个。阿巴卡韦总体耐受性良好，临床显著不良事件较少。两名受试者（3.3%）出现了对阿巴卡韦的过敏反应。各组在严重不良事件方面无差异。
对于未接受过抗逆转录病毒治疗的受试者，在第4周时，每日两次300mg或600mg阿巴卡韦治疗在统计学上优于每日两次100mg剂量。包含阿巴卡韦-齐多夫定-拉米夫定的联合治疗是一种高效的抗逆转录病毒方案，可使血浆HIV-1 RNA大幅下降，这可能与包含蛋白酶抑制剂的联合方案相当。阿巴卡韦总体耐受性良好。
