Both
infection with the human immunodeficiency virus type 1 (HIV) and
zidovudine (formerly called
azidothymidine [AZT]) cause
myopathy. To identify criteria for distinguishing
zidovudine-induced
myopathy from that caused by primary
HIV infection, we reviewed the histochemical, immunocytochemical, and electron-microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with
myopathy (15 of whom had been treated with
zidovudine) and compared the findings with the patients'
clinical course and response to various
therapies. Among the
zidovudine-treated patients, the
myopathy responded to
prednisone in four, to the discontinuation of
zidovudine in eight, and to nonsteroidal anti-inflammatory drugs in two. Numerous "ragged-red" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the
zidovudine-treated patients but not in those from the other patients. The number of these fibers appeared to correlate with the severity of the
myopathy. All the patients, regardless of whether they had been treated with
zidovudine, had
inflammatory myopathy characterized by degenerating fibers, cytoplasmic bodies, and endomysial infiltrates consisting of CD8+ cells (mean +/- SD, 60.7 +/- 6.4 percent) and macrophages (39.2 +/- 6.4 percent) associated with Class I major histocompatibility complex (MHC-I)
antigens (HLA-A, -B, and -C
antigens) in the muscle fibers. The numbers and percentages of CD8+ cells and macrophages were similar in both the
zidovudine-treated and the untreated HIV-positive patients. Specimens obtained on repeat muscle biopsy from two patients in whom the
myopathy responded to the discontinuation of
zidovudine showed remarkable histologic improvement. We conclude that long-term
therapy with
zidovudine can cause a toxic
mitochondrial myopathy, which coexists with a T-cell-mediated
inflammatory myopathy that is restricted to MHC-
I antigen, and is indistinguishable from the
myopathy associated with primary
HIV infection or
polymyositis in HIV-seronegative patients.