Saag M S, Sonnerborg A, Torres R A, Lancaster D, Gazzard B G, Schooley R T, Romero C, Kelleher D, Spreen W, LaFon S
Department of Medicine, University of Alabama at Birmingham, 35294-2050, USA.
AIDS. 1998 Nov 12;12(16):F203-9. doi: 10.1097/00002030-199816000-00002.
To evaluate, over 12 weeks, the antiretroviral activity and safety of abacavir, used alone and in combination with zidovudine (ZDV), as treatment for HIV-1-infected subjects who had limited or no antiretroviral treatment.
Seventy-nine HIV-1-infected subjects, with CD4 cell counts 200-500 x 10(6)/l and <12 weeks of previous treatment with ZDV were enrolled in a multicenter study. Subjects were randomly assigned to one of four cohorts receiving abacavir monotherapy for the first 4 weeks (200, 400, or 600 mg every 8 h daily, or 300 mg every 12 h daily) and, thereafter, combination therapy of abacavir with 600 mg ZDV or ZDV placebo, administered in a double-blind manner for an additional 8 weeks.
Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4+ cell counts. Safety was assessed by monitoring clinical adverse events and laboratory abnormalities during the 12-week period and for 4 weeks post-treatment.
Treatment with abacavir, alone or in combination with ZDV, produced marked decreases in plasma HIV-1 RNA loads and increases in CD4+ cell counts in all groups. At week 4, median plasma HIV-1 RNA loads decreased by 1.11-1.77 log10 copies/ml and median CD4+ cell counts increased by 63-111 x 10(6)/l in all groups. At week 12, median HIV-1 RNA loads decreased by 1.02-2.24 log10 copies/ml (abacavir monotherapy) and by 1.81-2.01 log10 copies/ml (abacavir-ZDV); median CD4+ cell counts increased by 79-195 x 10(6)/l (abacavir monotherapy) and by 93-142 x 10(6)/l (abacavir-ZDV). At week 12, the percentage of subjects who had plasma HIV-1 RNA levels below 400 and 40 copies/ml were 28 and 11%, respectively (abacavir monotherapy) and 69 and 22%, respectively (abacavir-ZDV). Eight subjects (10%) discontinued the study prematurely because of adverse events; nausea (n = 4) and hypersensitivity (n = 3) were the most common reasons for withdrawal. There were no deaths among the study subjects.
In HIV-infected subjects who have received little or no prior antiretroviral therapy, treatment with abacavir alone or in combination with ZDV is well tolerated and resulted in sustained improvements in key immunologic and virologic efficacy parameters through 12 weeks.
在12周内评估阿巴卡韦单独使用及与齐多夫定（ZDV）联合使用时，对接受过有限抗逆转录病毒治疗或未接受过抗逆转录病毒治疗的HIV-1感染受试者的抗逆转录病毒活性和安全性。
79名HIV-1感染受试者，其CD4细胞计数为200 - 500×10⁶/l且之前接受ZDV治疗少于12周，被纳入一项多中心研究。受试者被随机分配到四个队列之一，在前4周接受阿巴卡韦单药治疗（每日每8小时200、400或600mg，或每日每12小时300mg），此后，阿巴卡韦与600mg ZDV或ZDV安慰剂进行联合治疗，以双盲方式再给药8周。
通过测量血浆HIV-1 RNA水平和CD4⁺细胞计数的变化来评估抗逆转录病毒活性。通过在12周期间及治疗后4周监测临床不良事件和实验室异常来评估安全性。
阿巴卡韦单独使用或与ZDV联合使用治疗后，所有组的血浆HIV-1 RNA载量均显著下降，CD4⁺细胞计数均增加。在第4周时，所有组的血浆HIV-1 RNA载量中位数下降了1.11 - 1.77 log₁₀拷贝/ml，CD4⁺细胞计数中位数增加了63 - 111×10⁶/l。在第12周时，HIV-1 RNA载量中位数下降了1.02 - 2.24 log₁₀拷贝/ml（阿巴卡韦单药治疗）和1.81 - 2.01 log₁₀拷贝/ml（阿巴卡韦 - ZDV）；CD4⁺细胞计数中位数增加了79 - 195×10⁶/l（阿巴卡韦单药治疗）和93 - 142×10⁶/l（阿巴卡韦 - ZDV）。在第12周时，血浆HIV-1 RNA水平低于400和40拷贝/ml的受试者百分比分别为28%和11%（阿巴卡韦单药治疗）以及69%和22%（阿巴卡韦 - ZDV）。8名受试者（10%）因不良事件提前退出研究；恶心（n = 4）和超敏反应（n = 3）是最常见的退出原因。研究受试者中无死亡病例。
在几乎未接受过或未接受过抗逆转录病毒治疗的HIV感染受试者中，阿巴卡韦单独使用或与ZDV联合使用耐受性良好，并在12周内使关键的免疫和病毒学疗效参数持续改善。
