title: The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study.
abstract: OBJECTIVE
  To describe the use of second line protease-inhibitor (PI) regimens across Europe and to determine factors associated with virological and immunological response.
  
  
  METHODS
  Analysis of data from 984 patients with a median follow-up of 21 months enrolled in EuroSIDA. Patients started their second PI-containing regimen at least 16 weeks after starting the first PI-containing regimen and with viral load > 1000 copies/ml.
  
  
  METHODS
  Virological response was defined as a viral load < 500 copies/ml and immunological response as an increase of 50 x 10(6)/l or more in CD4 lymphocyte count.
  
  
  RESULTS
  The median CD4 cell count at starting the second PI was 171 x 10(6) cells/l; viral load was 4.45 log copies/ml. As a second PI regimen, 45% were using a dual PI, while of those on one PI, indinavir (42%) and nelfinavir (34%) were most common. In multivariate Cox models, a higher viral load at starting the second PI [relative hazard (RH), 0.67 per 1 log higher; 95% confidence interval (CI), 0.58-0.77; P < 0.0001) and a lower CD4 cell count (RH, 1.15 per 50% higher; 95% CI, 1.06-1.26; P = 0.0014) were associated with a reduced probability of virological response. Those who had achieved viral suppression on the first PI-regimen were more likely to respond to the second (RH, 1.65; 95% CI, 1.30-2.10; P < 0.0001) as were those who added one or two new nucleosides to their second PI.
  
  
  CONCLUSIONS
  Patients who initiate a second PI regimen at lower viral load, higher CD4 cell count or who added new nucleosides tended to be more likely to achieve a viral load < 500 copies/ml. The roles of cross-resistance and adherence in response to second-line regimens needs further investigation.
authors.affiliation: Royal Free Centre for HIV Medicine, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Mocroft
authors.forename: A N
authors.initials: AN
authors.lastname: Phillips
authors.forename: V
authors.initials: V
authors.lastname: Miller
authors.forename: J
authors.initials: J
authors.lastname: Gatell
authors.forename: J
authors.initials: J
authors.lastname: van Lunzen
authors.forename: J M
authors.initials: JM
authors.lastname: Parkin
authors.forename: R
authors.initials: R
authors.lastname: Weber
authors.forename: B
authors.initials: B
authors.lastname: Roge
authors.forename: A
authors.initials: A
authors.lastname: Lazzarin
authors.forename: J D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008297:Male; D019888:Nelfinavir / Q000627:therapeutic use*; D011446:Prospective Studies; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir