title: Risk factors for urological symptoms in a cohort of users of the HIV protease inhibitor indinavir sulfate: the ATHENA cohort.
abstract: BACKGROUND
  Nephrolithiasis is a well-known complication of indinavir treatment and may result in urological symptoms ranging from renal colic to renal insufficiency.
  
  
  OBJECTIVE
  To obtain further knowledge regarding the incidence and risk factors of urological symptoms associated with indinavir sulfate use.
  
  
  METHODS
  This study was performed in the ATHENA (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) cohort of patients infected with human immunodeficiency virus (HIV) receiving antiretroviral therapy in the Netherlands. The incidence rate of urological symptoms was assessed in a subcohort of 1219 patients starting HIV protease inhibitor treatment after 1996. Urological symptoms were defined as an initial report of nephrolithiasis, renal colic, flank pain, hematuria, renal insufficiency, or nephropathy. Using multivariate Cox regression analysis, risk factors for urological symptoms during indinavir treatment were subsequently studied among the subset of 644 patients who started indinavir treatment after 1996.
  
  
  RESULTS
  The incidence of urological symptoms was 8.3 per 100 treatment-years for indinavir vs 0.8 per 100 treatment-years for other HIV protease inhibitors. Risk factors for urological symptoms during indinavir treatment were low weight (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1-3.9), low lean body mass (RR, 1.7; 95% CI, 1.0-2.9), undetectable HIV-1 RNA when starting indinavir treatment (RR, 3.2; 95% CI, 1.5-6.0), prior treatment change because of intolerance (RR, 2.4; 95% CI, 1.2-5.1), indinavir regimens of 1000 mg or more twice daily (RR, 3.1; 95% CI, 1.3-8.2), and warm environmental temperatures (RR, 3.9; 95% CI, 1.7-8.8). Risk estimates were highest among patients with a low lean body mass.
  
  
  CONCLUSIONS
  Increased alertness for urological symptoms is warranted for patients starting indinavir treatment, particularly among those with a low lean body mass, during indinavir regimens of 1000 mg or more twice daily, and in warm weather environments.
authors.affiliation: Pharmaco-Epidemiology Unit, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jeanne P
authors.initials: JP
authors.lastname: Dieleman
authors.forename: Miriam C J M
authors.initials: MC
authors.lastname: Sturkenboom
authors.forename: Marielle
authors.initials: M
authors.lastname: Jambroes
authors.forename: Inge C
authors.initials: IC
authors.lastname: Gyssens
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Jacob H
authors.initials: JH
authors.lastname: ten Veen
authors.forename: Gerrit
authors.initials: G
authors.lastname: Schrey
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Bruno H Ch
authors.initials: BH
authors.lastname: Stricker
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D016001:Confidence Intervals; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D019469:Indinavir / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D012307:Risk Factors; D013997:Time Factors; D014570:Urologic Diseases / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir