Been-Tiktak A M, Boucher C A, Brun-Vezinet F, Joly V, Mulder J W, Jost J, Cooper D A, Moroni M, Gatell J M, Staszewski S, Colebunders R, Stewart G J, Hawkins D A, Johnson M A, Parkin J M, Kennedy D H, Hoy J F, Borleffs J C
Department of Internal Medicine, Eijkman-Winkler Institute of Medical Microbiology, University Hospital, Utrecht, The Netherlands.
Int J Antimicrob Agents. 1999 Jan;11(1):13-21. doi: 10.1016/s0924-8579(98)00082-x.
The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4 cell counts between 50 and 350 cells/microl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (> 10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.
本研究的目的是调查三种地拉韦啶剂量方案或安慰剂与齐多夫定联合应用于已服用齐多夫定患者的安全性和抗病毒效果。89例有症状的HIV-1血清阳性个体，其CD4细胞计数在50至350个/微升之间，被纳入该试验。研究了联合治疗对病毒对齐多夫定和地拉韦啶敏感性的影响。死亡或出现或再次出现艾滋病界定疾病被视为临床终点。通过定量RNA检测确定，在抗逆转录病毒治疗方案中添加地拉韦啶可导致病毒载量显著但短暂下降。CD4+细胞计数无显著变化。联合治疗12周后，对齐多夫定的敏感性保持不变，而70%的患者对 地拉韦啶的敏感性大幅下降（>10倍）。研究期间有两名患者患艾滋病界定疾病。无死亡病例发生。总体而言，该药物似乎是安全的。皮疹是最常观察到的不良事件（52%）。在大多数患者中，皮疹要么自行消退，要么通过短期服用抗组胺药成功治疗。该化合物在HIV疾病治疗中的确切地位，特别是与其他抗逆转录病毒药物联合使用时，仍有待进一步探索。
