Hollander H, Lifson A R, Maha M, Blum R, Rutherford G W, Nusinoff-Lehrman S
Department of Medicine, University of California, San Francisco 94143.
Am J Med. 1989 Dec;87(6):628-32. doi: 10.1016/s0002-9343(89)80394-8.
The combination of zidovudine and acyclovir has shown in vitro antiretroviral activity and led to short-term improvement in patients with symptomatic human immunodeficiency disease (HIV) disease. We performed a phase I study of zidovudine (500 mg/day) plus acyclovir (2 or 4 g/day) in asymptomatic HIV-seropositive men to investigate pharmacokinetics, safety, tolerance, and immunologic effects of the combination.
Fifty HIV-seropositive homosexual or bisexual men from the San Francisco City Clinic Cohort Study were recruited for the study; of these, 20 met the eligibility criteria. Treatment with zidovudine and acyclovir was open label. Pharmacokinetic, virologic, immunologic, and clinical data were collected periodically over a 24-week period.
Pharmacokinetic analysis showed no drug interaction. The combination was generally well tolerated, and hematologic parameters remained stable through 24 weeks. There were no significant changes in total lymphocytes, T4 lymphocytes, overall skin test reactivity, or ability to culture virus from peripheral blood.
This combination of agents is safe in this population for at least six months. Conclusions about long-term tolerance and efficacy await the results of larger trials with longer follow-up.
齐多夫定与阿昔洛韦联合使用已显示出体外抗逆转录病毒活性，并使有症状的人类免疫缺陷病毒（HIV）病患者的病情得到短期改善。我们对无症状的HIV血清阳性男性进行了一项齐多夫定（500毫克/天）加阿昔洛韦（2或4克/天）的I期研究，以调查该联合用药的药代动力学、安全性、耐受性和免疫学效应。
从旧金山城市诊所队列研究中招募了50名HIV血清阳性的同性恋或双性恋男性参与研究；其中20名符合入选标准。齐多夫定和阿昔洛韦的治疗采用开放标签。在24周的时间内定期收集药代动力学、病毒学、免疫学和临床数据。
药代动力学分析显示无药物相互作用。该联合用药总体耐受性良好，血液学参数在24周内保持稳定。总淋巴细胞、T4淋巴细胞、总体皮肤试验反应性或从外周血中培养病毒的能力均无显著变化。
该药物组合在该人群中至少六个月是安全的。关于长期耐受性和疗效的结论有待更大规模、随访时间更长的试验结果。
