OCULAR TOXICITY OF 2',3'-DIDEOXYINOSINE

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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.