Skeletal muscle involvement in human immunodeficiency virus (HIV)–infected patients in the era of highly active antiretroviral therapy (HAART)

Abstract

Skeletal muscle involvement can occur at all stages of human immunodeficiency virus (HIV) infection, and may represent the first manifestation of the disease. Myopathies in HIV-infected patients are classified as follows: (1) HIV-associated myopathies and related conditions, including HIV polymyositis, inclusion-body myositis, nemaline myopathy, diffuse infiltrative lymphocytosis syndrome (DILS), HIV-wasting syndrome, vasculitic processes, myasthenic syndromes, and chronic fatigue; (2) muscle complications of antiretroviral therapy, including zidovudine and toxic mitochondrial myopathies related to other nucleoside-analogue reverse-transcriptase inhibitors (NRTIs), HIV-associated lipodystrophy syndrome, and immune restoration syndrome related to highly active antiretroviral therapy (HAART); (3) opportunistic infections and tumor infiltrations of skeletal muscle; and (4) rhabdomyolysis. Introduction of HAART has dramatically modified the natural history of HIV disease by controlling viral replication, but, in turn, lengthening of the survival of HIV-infected individuals has been associated with an increasing prevalence of iatrogenic conditions.

Whole-Body Proteolysis Rate Is Elevated in HIV-Associated Insulin Resistance

“…The mechanism is multifactorial and likely comprises the effects of chronic viral infection, host response, anti-HIV medications, genetics, lifestyle/behavioral factors on intracellular signaling pathways, and substrate partitioning and sensing (9,10). Several groups have reported that HIV-associated insulin resistance is characterized by perturbations in glucose and lipid metabolism, which are common to type 2 diabetes (11)(12)(13)(14)(15)(16)(17)(18)(19). Whether HIV-associated insulin resistance is associated with defects in amino acid and protein metabolism has not been addressed.…”

Inclusion body myositis and HIV infection

“…A direct link between NRTI, mitochondrial dysfunction, and IBM is strongly suggested in a case of IBM in HIV infection 7 NRTI prolonged use may contribute to the development of IBM in this type of patients. In these cases the discontinuation of NRTI may be a strategy for management, although whether the condition is reversible remain unknown 7 .…”

“…Retroviral antigens have been detected in endomysial macrophages but not within the muscle fibers 6,7 . The activated CD8+ cells invade muscle fibres expressing MHC class I, as seen in retrovirus-negative polymyositis and IBM 6,11 .…”

“…In these cases the discontinuation of NRTI may be a strategy for management, although whether the condition is reversible remain unknown 7 .…”

“…A variety of muscular disorders has been described in HIV infected patients 3 : polymyositis, myopathy induced by nucleoside reverse transcriptase inhibitors (NRTI), such as zidovudine, opportunistic infections including toxoplasmosis, infiltration by tumour, HIV associated vasculitis, and rhabdomyolysis caused by HIV itself or by drugs including didanosine 5 . A myopathy in every respect similar to inclusion body myositis (IBM) is observed in rare patients infected by HIV-1 or human T-cell leukaemia virus type 1(HTLV-1) 6,7 . IBM is a chronic inflammatory muscle disease, and the typical clinical findings are muscle weakness and atrophy, most prominent in the quadriceps muscles and the wrist and finger flexors 8 .…”