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the dose or interrupting therapy may help to resolve the neuropathy. NRTI-specific peripheral
neuropathy may be reversible when the drug is stopped.[808,812] Patients receiving protease
inhibitor therapy may develop an HIV-associated sensory neuropathy-SN, which may potentiate
neuronal damage in HIV-infected dorsal root ganglia, and this may occur from loss of
macrophage-derived trophic factors.[271]

SKELETAL MUSCLE.— HIV-associated myopathy can occur at any stage of HIV
infection and has clinical and histopathologic features similar to those of polymyositis (PM).
Affected persons have proximal, diffuse, and often symmetric muscle weakness that develops
subacutely, over weeks to months, without cutaneous rash or involvement of the extraocular and
facial muscles. Myalgias seem more frequent than in classic PM patients. EMG typically reveals
abnormal spontaneous activity with posi-tive sharp waves, fibrillations, and low-amplitude and
short-duration polyphasic motor unit action potentials., but patients may also have a normal
EMG. Serum creatine kinase (CK) levels are usually increased, but may not correlate with
disease severity. Muscle biopsy shows the characteristic triad of scattered necrotic and
basophilic fibers, multiple foci of mononuclear inflammatory cells within fascicles, and focal
invasion of non-necrotic muscle fibers by CD8 lymphocytes.[813,814]
The immunohistochemical staining to establish the diagnosis of PM includes: (1)
endomysial infiltrates of activated CD8+ T cells; (2) ubiquitous sarcolemmal expression of MHC
class I antigens by muscle fibers; and (3) focal invasion of non-necrotic fibers expressing MHC-I
by CD8+ T cells, a condition termed MHC-I/CD8 complex. An autoimmune etiology has been
postulated, and is substantiated by the benefit afforded by corticosteroid therapy, non-steroidal
anti-inflammatory agents, plasma exchange, or intravenous immunoglobulin therapy.[813,814]
Another form of HIV-associated myopathy is known as human immunodeficiency virus
associated adult onset nemaline myopathy (HAONM). On muscle biopsy the skeletal muscle
fibers in HAONM show marked intra sarcoplasmic changes, including the presence of small
vacuoles and granular degeneration, along with prominent, randomly distributed atrophic type 1
fibers with numerous intracytoplasmic rod bodies in the centers of the fibers, corresponding to
the nemaline rods seen with electron microscopy. Necrotic fibers and inflammatory infiltrates are
usually not found. Some patients may have a monoclonal gammopathy in association with this
nemaline myopathy.[814]
Myopathy can be associated with nucleoside reverse transcriptase inhibitor (NRTI)
therapy, including zidovudine (AZT) and stavudine therapy. The appearance of this myopathy is
related to a longer course of therapy (months). It is estimated to occur in 0.4% of persons
receiving AZT. Patients present with insidious pelvic and shoulder girdle muscular weakness
with myalgia. Serum creatine kinase is increased 2 to 6 times normal. Cessation of the drug
leads to reversal and recovery in weeks to months, with earlier recovery when weakness is less
severe.[812,813] The toxic effect appears to be directed at mitochondria, resulting in the
hematoxylin-eosin-stained appearance of "ragged red" fibers.[259] Two-thirds of AIDS cases at
autopsy reveal histologic abnormalities including disuse atrophy, denervation atrophy, and
inflammatory myopathy, though opportunistic infections are rarely found.[815]
Sporadic inclusion body myositis, which is the most common inflammatory myopathy in
persons over the age of 50, has been reported in association with HIV infection. The persistent
HIV infection may provide super antigenic stimulation that results in an endomysial
inflammatory response. HIV-1 has been detected within endomysial macrophages, but not the
muscle fibers, indicating that retroviruses do not directly infect muscle but trigger an immune