Low-dose zalcitabine-related toxic neuropathy: frequency, natural history, and risk factors.
We studied the features and frequency of sensory neuropathy among 79 HIV-1-infected individuals participating in a multicenter clinical trial of zalcitabine (2'3'-dideoxycytidine, or ddC) antiretroviral therapy. The trial compared zalcitabine monotherapy (2.25 mg/day) versus combination 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 alone--a 7.9-fold increase in the attack rate of neuropathy. Using risk factor analysis, we found that diabetes mellitus was significantly associated with the development of toxic neuropathy (p = 0.02), and weight loss may contribute to its appearance. Like HIV-associated sensory neuropathy, ddC-related toxic neuropathy is a predominantly sensory, length-dependent, symmetric, painful neuropathy. Dose reduction lessened the severity of symptoms, although objective signs of neuropathy persisted. Patients with subclinical neuropathies or significant neuropathy risks such as diabetes may be poor candidates for ddC therapy.
Blum
A S
AS
Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Dal Pan
G J
GJ
Feinberg
J
J
Raines
C
C
Mayjo
K
K
Cornblath
D R
DR
McArthur
J C
JC
D000328:Adult; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D012307:Risk Factors; D012678:Sensation Disorders / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D016019:Survival Analysis; D016047:Zalcitabine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use
D016047:Zalcitabine