Reversible axonal neuropathy from the treatment of AIDS and related disorders with 2′,3′‐dideoxycytidine (ddc)

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Abstract
A total of 20 patients with acquired immune deficiency syndrome (AIDS) or AIDS‐related complex (ARC) received the anti‐retroviral drug 2′,3′,dideoxycytidine in a phsae I study at doses ranging from 0.03 mg/kg every 8 hours to 0.25 mg/kg every 8 hours. Of the 11 patients who participated in the study for more than 5 weeks, 9 developed symptoms and signs of a mainly sensory painful neuropathy that was confirmed by electromyography to be mixed sensory and motor neuropathy of axonal type. The neuropathy which developed on dideoxycytidine occurred between 9 and 12 weeks of treatment. One patient, who had the drug stopped at 3 weeks owing to thrombocytopenia, developed a similar clinical picture of a sensory peripheral neuropathy after 2 weeks off dideoxycytidine. However, he did not have electromyographic evidence of a neuropathy, and he subsequently returned to normal clinically while taking a lower dose of dideoxycytidine in an alternating regimen. Five patients were withdrawn from the study because of the neuropathy. The pattern of this neuropathy was different from that of the slowly progressive painful neuropathy of AIDS, in that there was (1) a sudden onset of intense burning discomfort in both feet sparing the hands at about the tenth week (mean 10.4 weeks) of treatment, (2) there was motor involvement in some patients without progression, and (3) onset of the neuropathy was temporally related to the administration of dideoxycytidine and began to resolve 3–5 weeks after its discontinuation. We believe that dideoxycytidine can be an axonal toxin, especially when given in high dose continuous regimens. We are now exploring whether a low‐dose regimen or regimens that incorporate a drug rest period can obviate this toxicity.