OCULAR TOXICITY OF 2',3'-DIDEOXYINOSINE

2 '，3'-二脱氧肌苷（ddI），一种具有抗逆转录病毒活性的嘌呤类似物 用于治疗获得性免疫缺陷综合征（AIDS）患者， 在NIH临床方案中被用于治疗成人和儿童。 本研究的目的是前瞻性随访接受DDI治疗的患者， 继发于药物毒性的眼部并发症的发生。 95名有症状的儿童中有4名（疾病控制中心 P-2类）艾滋病毒感染者参加了一项I-II期研究，以评估 ddI的安全性和抗逆转录病毒活性， 视网膜色素上皮细胞（RPE）在ddI治疗。两 患有最严重视网膜萎缩的<$IChildren>儿童被纳入 在研究的最高剂量水平（540 mg/m2/天）下进行研究。 3例视网膜病变患者中有1例眼电图异常， 可以测试的毒性。15名接受ddI治疗的成年人正在接受 随后定期进行眼底检查和眼电图检查。在 与儿童的结果相反，没有证据表明视网膜 迄今为止，在接受ddI治疗的HIV感染成人中的毒性。 在大鼠RPE细胞、大鼠肺细胞系 CCL 149和人羊水细胞系WISH。短期毒性 研究中，ddI没有改变细胞活力，如锥虫试验所示。 蓝色排斥或细胞增殖，通过总活细胞测定 随着时间的推移而计算。未来的体外毒性研究将在 人RPE细胞。 此外，放射性标记的DDI将用于评价 RPE细胞和其他细胞摄取的ddI浓度。

2',3'-dideoxyinosine (ddI), a purine analog with antiretroviral activity used to treat patients with the acquired immune deficiency syndrome (AIDS), is being used to treat both adults and children in NIH clinical protocols. The purpose of this study is to follow prospectively ddI-treated patients for the development of ocular complications secondary to drug toxicity. Four of ninety-five children with symptomatic (Centers for Disease Control class P-2) HIV infection enrolled in a phase I-II study to assess the safety and antiretroviral activity of ddI developed peripheral atrophy of the retinal pigment epithelium (RPE) during ddI therapy. The two <$IChildren>children with the most severe retinal atrophy were enrolled in the study at the highest dose level studied (540 mg/m2/day). Electrooculograms were abnormal in one of three patients with retinal toxicity who could be tested. Fifteen adults treated with ddI are being followed with periodic fundus examinations and electrooculograms. In contrast to results in children, there has been no evidence of retinal toxicity in HIV-infected adults treated with ddI to date. The effects of ddI were evaluated on rat RPE cells, the rat lung cell line CCL 149, and on the human amnion cell line WISH. In short-term toxicity studies, ddI did not alter either cell viability, as determined by trypan blue exclusion, or cell proliferation, as assayed by total viable cell counts over time. Future in vitro toxicity studies will be performed on human RPE cells. In addition, radiolabeled ddI will be used to evaluate the concentration of ddI taken up by RPE cells and other cells.