Neuromuscular function in HIV infection: analysis of a placebo-controlled combination antiretroviral trial

Objective: To determine the frequency of peripheral neuropathy and myopathy in HIV-infected subjects enrolled in a combination antiretroviral treatmen t trial. Design and methods: AIDS Clinical Trial Group (ACTG) protocol 175 was a mul ticenter, double-blind, placebo-controlled, clinical trial. A total of 2467 subjects were randomized to one of four single or combination regimens, co ntaining zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), and their r espective placebos. Site investigators reported peripheral neuropathy, and the diagnosis of distal symmetrical neuropathy (DSP) was established by the study authors. Myalgia, muscle weakness and creatine phosphokinase (CPK) w ere prospectively assessed in a subset of the antiretroviral-naive cohort(n = 1067). Results: Of 222 site diagnoses of neuropathy, 109 (49%) were DSP. There was a significant difference between treatment arms for rate of DSP and time t o first grade 2 or higher DSP (ZDV-ddC, 6%; ZDV, 4%; ZDV-ddl, 4%; ddl, 3%; P = 0.029). Age and Karnofsky score were significant predictors of DSP. Fif ty-six (54%) out of 104 patients with DSP remained on study medication at f ull (n = 29) or reduced (n = 27) dose within 6 months of developing neuropa thy. There was no significant difference between treatment arms in the rate of myalgia or muscle weakness. The median CPK of subjects on ZDV-ddC was s ignificantly higher than other study treatments, although CPK levels did no t correlate with symptoms of myopathy. Only six subjects were diagnosed wit h myopathy during the study (one ZDV-ddl, one ZDV-ddC, and four ddl). Conclusions: DSP and myopathy may occur with current dosing regimens of com bination antiretroviral therapy, and should be diagnosed using stringent cr iteria. ZDV-ddC was associated with the highest rate of DSP, although featu res of myopathy were not significantly different between treatment regimens . (C) 1998 Lippincott Williams & Wilkins.