title: Factors predictive of successful darunavir/ritonavir-based therapy in highly antiretroviral-experienced HIV-1-infected patients (the DARWEST study).
abstract: BACKGROUND
  Darunavir (DRV) is the latest protease inhibitor (PI) to be approved for antiretroviral-naive and -experienced HIV-infected patients.
  
  
  OBJECTIVE
  We examined virologic and immunologic outcomes of highly antiretroviral-experienced patients with triple-class drug resistance receiving DRV/r-based regimens, and attempted to identify factors predictive of virologic success.
  
  
  METHODS
  We studied patients beginning a ritonavir-boosted DRV (DRV/r 600/100mg twice daily)-containing regimen. Virologic success was defined as plasma viral load (pVL)<50copies/ml at week 36.
  
  
  RESULTS
  We studied 62 patients with very severe immunodeficiency (CDC stage C in 69% of cases; median CD4 cell nadir 12/mm(3)). They had previously received a median of four PI and had extensive PI resistance, with a median of three major PI and two DRV resistance mutations. The baseline median pVL and CD4 cell count values were 4.6log(10) and 150/mm(3). At week 36, pVL had fallen by 2.6log(10) and the CD4 cell count had risen by 123cells/mm(3). The virologic success rate was 55% overall, and was improved by concomitant first use of enfuvirtide (67%), raltegravir (69%) or etravirine (75%). Virologic success was independently associated with fewer major PI mutations, previous tipranavir exposure, and concomitant first use of enfuvirtide or raltegravir.
  
  
  CONCLUSIONS
  In these highly antiretroviral-experienced patients with triple-class drug resistance, virologic success of DRV-containing regimens was mainly associated with the use of new drug classes and/or fully active drugs. Interestingly, previous tipranavir failure did not undermine the efficacy of DRV, confirming the low level of cross-resistance and, probably, distinct resistance profiles between DRV and tipranavir.
authors.affiliation: Department of Virology, Saint Louis Hospital-APHP, 75010 Paris, France. constance.delaugerre@sls.aphp.fr
authors.forename: C
authors.initials: C
authors.lastname: Delaugerre
authors.forename: J F
authors.initials: JF
authors.lastname: Buyck
authors.forename: G
authors.initials: G
authors.lastname: Peytavin
authors.forename: J P
authors.initials: JP
authors.lastname: Viard
authors.forename: M L
authors.initials: ML
authors.lastname: Chaix
authors.forename: D
authors.initials: D
authors.lastname: Zucman
authors.forename: E
authors.initials: E
authors.lastname: Mortier
authors.forename: S
authors.initials: S
authors.lastname: Blanche
authors.forename: E
authors.initials: E
authors.lastname: Rouveix
authors.forename: G
authors.initials: G
authors.lastname: Force
authors.forename: P
authors.initials: P
authors.lastname: Aegerter
authors.forename: P
authors.initials: P
authors.lastname: de Truchis
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir