OCULAR TOXICITY OF 2',3'-DIDEOXYINOSINE

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2',3'-Dideoxyinosine (ddI) is a purine analog with antiretroviral activity currently used to treat patients with the acquired immunodeficiency syndrome (AIDS). ddI is being used to treat both adults and children in clinical protocols at NIH. The purpose of this study is to follow patients treated with ddI prospectively and observe the development of ocular complications secondary to drug toxicity. Of 95 children with symptomatic (CDC class P-2) HIV infection enrolled in a phase I-II study to assess the safety and antiretroviral activity of ddI, 5 developed peripheral atrophy of the retinal pigment epithelium during ddI therapy. The two children with the most severe retinal atrophy were enrolled in the study at the highest dose level studied (540 mg/m-squared/day). Electro-oculograms were abnormal in one of three patients with retinal toxicity who could be tested. A group of 75 adults treated with ddI are being followed with periodic fundus examinations and electro-oculograms. In contrast to the results in children, there has been no evidence of retinal toxicity in HIV-infected adults treated with ddI. The effects of ddI were evaluated on rat retinal pigment epithelial (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 cell viability, as determined by trypan blue exclusion, or cell proliferation, 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 and other cells.