Neuromuscular function in HIV infection: analysis of a placebo-controlled combination antiretroviral trial. AIDS Clinical Group 175/801 Study Team

AIDS. 1998 Dec 24;12(18):2425-32. doi: 10.1097/00002030-199818000-00011.

Abstract

Objective: To determine the frequency of peripheral neuropathy and myopathy in HIV-infected subjects enrolled in a combination antiretroviral treatment trial.

Design and methods: AIDS Clinical Trial Group (ACTG) protocol 175 was a multicenter, double-blind, placebo-controlled, clinical trial. A total of 2467 subjects were randomized to one of four single or combination regimens, containing zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), and their respective 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) were 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 to 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. Fifty-six (54%) out of 104 patients with DSP remained on study medication at full (n = 29) or reduced (n = 27) dose within 6 months of developing neuropathy. 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 significantly higher than other study treatments, although CPK levels did not correlate with symptoms of myopathy. Only six subjects were diagnosed with myopathy during the study (one ZDV-ddl, one ZDV-ddC, and four ddl).

Conclusions: DSP and myopathy may occur with current dosing regimens of combination antiretroviral therapy, and should be diagnosed using stringent criteria. ZDV-ddC was associated with the highest rate of DSP, although features of myopathy were not significantly different between treatment regimens.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Creatine Kinase / metabolism
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Muscular Diseases / chemically induced
  • Muscular Diseases / diagnosis
  • Muscular Diseases / etiology*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / etiology*
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Creatine Kinase