A variety of disorders of peripheral nerve or muscle may occur in association with HIV infection. Neuromuscular diseases may result in pain, loss of sensation, and profound weakness. Muscle disease (i.e., myopathy) is under-recognized for several reasons, including the fact that weakness is often attributed simply to the ravages of HIV infection. HIV-associated myopathy is a treatable neuromuscular disorder with distinct clinical, laboratory and histopathological features. In some patients this myopathy underlies HIV wasting syndrome.

Several investigators have noted that AZT therapy may cause myopathy, prompting clinicians to halt this therapy when muscle weakness occurs. However, the data used to support this association were gathered retrospectively, without control groups, with variable diagnostic criteria for myopathy and with inconsistent clinical response to AZT withdrawal. In addition, corticosteroid therapy has been effective in some cases, although this has not been evaluated in a scientific trial.

The proposed 3-year project includes two studies: (a) a longitudinal study of HIV-infected individuals with semi-annual clinical and quantitative neuromuscular examinations and (b) randomized, controlled clinical trials of AZT withdrawal and corticosteroid therapy in patients with myopathy. These studies will address the following issues: (1) Determination of neuromuscular disorders in HIV-infected individuals utilizing a variety of clinical, serological, quantitative motor and neurophysiological techniques; (2) Utility of various tools in diagnosis of myopathy, as correlated with muscle biopsy; (3) Ability of muscle biopsy to discriminate between myopathies caused by AZT and HIV; (4) Efficacy of AZT withdrawal in resolution of myopathy via a randomized placebo-controlled trial; (5) Utility of corticosteroid therapy for debilitating myopathy via a randomized, placebo-controlled trial; (6) Effects of the degree of immunologic impairment and nutritional status on the occurrence and progression of neuromuscular disease.

Recent evidence indicates that HIV-infected persons can benefit from AZT therapy early in the course of their disease. Therefore, substantially more people will be taking AZT for longer periods of time, increasing their likelihood of developing AZT toxicity. Furthermore, with the recent introduction of alternate antiretroviral agents, i.e. DDI, it would be of subtantial clinical benefit to define markers of HIV and AZT myotoxicity and paradigms for their management.

R01NS028630

1990-12-01

1994-11-30