title: Creatine kinase elevation in HIV-1-infected patients receiving raltegravir-containing antiretroviral therapy: a cohort study.
abstract: OBJECTIVE
  To evaluate the incidence and risk factors for significant creatine kinase elevation in HIV-1-infected patients who were prescribed a raltegravir-containing antiretroviral therapy.
  
  
  METHODS
  A retrospective analysis of a prospectively collected cohort involving all consecutive patients who were prescribed a raltegravir-containing antiretroviral regimen between June 2005 and December 2010.
  
  
  METHODS
  Significant creatine kinase elevation was defined as an elevation of at least 3-fold from the upper limit of normal (ULN) (grade 2, WHO classification) while receiving raltegravir. Blood analysis at each visit included at least creatine kinase, as well as plasma HIV-1 RNA and CD4 cell count.
  
  
  RESULTS
  There were 475 patients who had been exposed to raltegravir for a median of 11.5 (IQR 8.2-15.2) months. An increase of creatine kinase ≥ 3-fold ULN was detected in 53 (11.2%) patients, representing an incidence of 3.8/100 person-years. Symptoms were reported by seven patients (1.5%), they showed either grade 1 (n = 3) or 2 (n = 4) creatine kinase increases. The median duration of raltegravir therapy before creatine kinase elevation was 5.9 (IQR 3.3-9.3) months. Evidence of creatine kinase elevation prior to raltegravir therapy [hazard ratio (HR) 3.30; 95% CI 1.59 ± 6.86; P = 0.001], abnormal baseline creatine kinase (HR 3.24; 95% CI 1.63 ± 6.45; P = 0.001) and male gender (HR 4.17; 95% CI 1.33 ± 1.27; P = 0.001) were identified as independent risk factors for creatine kinase elevation during raltegravir treatment.
  
  
  CONCLUSIONS
  Although ≈ 1 in 10 patients on raltegravir therapy developed significant creatine kinase elevation as defined in this study, symptoms were uncommon, not severe and occurred in patients with easily identifiable risk factors.
authors.affiliation: Hospital Clínic-IDIBAPS, University of Barcelona, 08036 Barcelona, Spain. polymonteiro@hotmail.com
authors.forename: Polyana
authors.initials: P
authors.lastname: Monteiro
authors.forename: Iñaki
authors.initials: I
authors.lastname: Perez
authors.forename: Judit
authors.initials: J
authors.lastname: Pich
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Gatell
authors.forename: Esteban
authors.initials: E
authors.lastname: Martínez
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D001774:Blood Chemical Analysis; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003402:Creatine Kinase / Q000097:blood*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D012189:Retrospective Studies
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D003402:Creatine Kinase