LOW-DOSE ZALCITABINE-RELATED TOXIC NEUROPATHY - FREQUENCY, NATURAL-HISTORY, AND RISK-FACTORS

We studied the features and frequency of sensory neuropathy among 79 H IV-1-infected individuals participating in a multicenter clinical tria l of zalcitabine (2'3'-dideoxycytidine, or ddC) antiretroviral therapy . The trial compared zalcitabine monotherapy (2.25 mg/day) versus comb ination therapy (2.25 mg/day ddC) with zidovudine (ZDV, formerly AZT) versus monotherapy with ZDV alone. Neuropathy developed in 34% of ddC recipients but in only 4% of comparable patients treated with ZDV alon e-a 7.9-fold increase in the attack rate of neuropathy. Using risk fac tor analysis, we found that diabetes mellitus was significantly associ ated with the development of toxic neuropathy (p = 0.02), and weight l oss may contribute to its appearance. Like HIV-associated sensory neur opathy, ddC-related toxic neuropathy is a predominantly sensory, lengt h-dependent, symmetric, painful neuropathy. Dose reduction lessened th e severity of symptoms, although objective signs of neuropathy persist ed. Patients with subclinical neuropathies or significant neuropathy r isks such as diabetes may be poor candidates for ddC therapy.