Skeletal muscle damage: emerging toxicity of HIV therapy?

An unexpectedly high incidence of enzyme elevations indicating muscle damage in patients receiving highly active antiretroviral therapy (HAART) have been reported by Italian researchers at the University of Bologna.

The group, led by Roberto Manfredi, told the Sixth International Congress on Drug Therapy in HIV Infection that 15% of their 879 patient cohort receiving anti-HIV therapy had elevations in creatine phosphokinase.

Creatine phosphokinase (CPK) is an enzyme found mainly in the brain, heart and skeletal muscle. When total CPK levels are substantially elevated, it usually indicates injury or stress to one or more of these areas.

The group conducted a case control study to identify factors that might be associated with CPK elevations.

Thirty-seven (28%) of patients with CPK elevations reported muscle weakness or fatigue, compared to 103 (26%) of patients without CPK elevations, but 5 cases of myositis (inflammation and destruction of muscle tissue) or rhabdomyolysis (muscle cell destruction) were reported among patients with elevated CPK levels, compared with none in the group with normal CPK levels.

Patients were analysed according to duration of HIV infection, age, gender, AIDS diagnosis, hepatitis co-infection, viral load, current CD4 cell count, lipodystrophy, hyperlipidemia, lipid-lowering treatment, bone problems, liver enzyme elevations, duration of HAART and exposure to each of the nucleoside analogues.

The only factors significantly associated with CPK elevations were male gender (p<0.001) and d4T treatment (p<0.006).

CPK elevation has been reported previously in clinical trials of most nucleoside analogues, and muscle damage was particularly associated with AZT treatment using higher doses than those taken today.

The authors of the study say that alterations of skeletal muscle tissue, although mainly asymptomatic, may represent an emerging and underestimated toxicity in HIV patients that deserve further investigation.