title: Skeletal muscle toxicity associated with raltegravir-based combination antiretroviral therapy in HIV-infected adults.
abstract: OBJECTIVE
  Raltegravir is uncommonly associated with rhabdomyolysis and grade 3-4 creatine kinase (CK) elevation. In this cross-sectional study, we compared the prevalence of skeletal muscle toxicity in HIV-infected adults receiving raltegravir with that of a control group.
  
  
  METHODS
  Adults receiving combination antiretroviral therapy were recruited consecutively. Assessments included physical examination, an exercise questionnaire, and blood testing for CK, troponin T, and raltegravir trough levels. The primary endpoint was the prevalence of skeletal muscle toxicity, defined as a composite of any of the following: (1) isolated CK elevation; (2) myalgia; (3) proximal myopathy on examination; or (4) rhabdomyolysis.
  
  
  RESULTS
  A total of 318 participants (159 raltegravir, 159 control) were evaluated; 98% were male, 89% white, with median age 51 years, and 91% had HIV-1 RNA <50 copies per milliliter. Mean raltegravir exposure was 28 months. Skeletal muscle toxicity was present in 37% of the raltegravir vs. 19% of the control group (P < 0.001). By component, there were significant respective differences in myalgia (19% vs. 3%, P < 0.001) and proximal myopathy (4% vs. 0%, P = 0.030) but not CK elevation (14% vs. 16%, P = 0.639). No patient had rhabdomyolysis. In multivariate analysis, raltegravir therapy (P < 0.001) and strenuous exercise (P = 0.002) were independently associated with overall muscle toxicity. No component of muscle toxicity was associated with duration of raltegravir or the raltegravir level.
  
  
  CONCLUSIONS
  Raltegravir-based therapy is associated with a higher prevalence of symptomatic skeletal muscle toxicity, which does not seem to be concentration or time dependent, nor associated with elevated CK. Proximal myopathy may be an uncommon but significant side effect of raltegravir exposure.
authors.affiliation: Clinical Research Program, St. Vincent's Centre for Applied Medical Research, Sydney, Australia. flee3@stvincents.com.au
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Lee
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Pett
authors.forename: Debbie
authors.initials: D
authors.lastname: Marriott
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D003402:Creatine Kinase / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009135:Muscular Diseases / Q000097:blood / Q000139:chemically induced* / Q000201:enzymology; D011760:Pyrrolidinones / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D020107:Troponin T / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D020107:Troponin T; D000068898:Raltegravir Potassium; D003402:Creatine Kinase