title: Determinants of recurrent toxicity-driven switches of highly active antiretroviral therapy. The ATHENA cohort.
abstract: BACKGROUND
  Toxicity is the most important reason for premature switching of highly active antiretroviral therapy (HAART). In order to optimize the benefit-risk ratio of HAART, guidelines for toxicity management are needed.
  
  
  OBJECTIVE
  An observational cohort study to estimate the incidence and identify determinants of toxicity-driven switches on second-line HAART after having switched first-line HAART despite successful viral suppression.
  
  
  METHODS
  Patients were selected from those in the ATHENA cohort (n = 2470) who switched the initial HIV protease inhibitor (PI)-containing HAART while plasma HIV-1 RNA was <or= 500 copies/ml (n = 775). One-year cumulative incidences of subsequent toxicity-driven switches and adjusted relative risks (RR) for potential determinants were calculated.
  
  
  RESULTS
  The 1-year cumulative incidence of toxicity-driven switches of the second regimen was 24% [95% confidence interval (CI), 21-28], mostly because of gastrointestinal toxicity and neuropathy. Those who had switched from first HAART because of toxicity were at an increased risk of a recurrent toxicity-driven switch (RR, 2.5; 95% CI, 1.7-3.5). Switching from PI to nevirapine while continuing the other antiretroviral drugs was more protective against a subsequent switch because of further toxicity than changing to another PI-containing regimen (RR, 0.2; 95% CI, 0.1-0.6).
  
  
  CONCLUSIONS
  As for first-line HAART, toxicity is responsible for the majority of switches during second-line HAART. Prior switching for toxicity increased the risk of having to switch the subsequent regimen for toxicity, but this risk is reduced when switching to nevirapine rather than to an alternative PI. The latter should be taken into account when designing toxicity-management guidelines.
authors.affiliation: the Pharmaco-Epidemiology Unit, Departments of Internal Medicine, and Epidemiology & Biostatistics, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.
authors.forename: Jeanne P
authors.initials: JP
authors.lastname: Dieleman
authors.forename: Marielle
authors.initials: M
authors.lastname: Jambroes
authors.forename: Inge C
authors.initials: IC
authors.lastname: Gyssens
authors.forename: Miriam C J M
authors.initials: MC
authors.lastname: Sturkenboom
authors.forename: Bruno H Ch
authors.initials: BH
authors.lastname: Stricker
authors.forename: Wilhelmina M C
authors.initials: WM
authors.lastname: Mulder
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Gerrit-Jan
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Kees
authors.initials: K
authors.lastname: Brinkman
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors