title: Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials.
abstract: BACKGROUND
  The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate efficacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs).
  
  
  METHODS
  After 24-week dose-finding phases and primary efficacy analyses, patients randomised to receive darunavir-ritonavir were given 600/100 mg twice daily, and patients receiving control PIs continued on assigned treatment into the longer-term, open-label phase; all patients continued on optimised background regimen. We assessed patients who had reached week 48 or discontinued earlier at the time of analysis; for the darunavir-ritonavir group, only patients who received 600/100 mg twice daily from baseline were included. Analyses were intention-to-treat. The POWER 2 study (TMC114-C202) is registered with ClinicalTrials.gov (NCT00071097).
  
  
  RESULTS
  At week 48, 67 of 110 (61%) darunavir-ritonavir patients compared with 18 of 120 (15%) of control PI patients had viral load reductions of 1 log10 copies per mL or greater from baseline (primary endpoint; difference in response rates 46%, 95% CI 35%-57%, p<0.0001). Based on a logistic regression model including stratification factors (baseline number of primary PI mutations, use of enfuvirtide, baseline viral load) and study as covariates, the difference in response was 50% (odds ratio 11.72, 95% CI 5.75-23.89). In the darunavir-ritonavir group, rates of adverse events were mostly lower than or similar to those in the control group when corrected for treatment exposure. No unexpected safety concerns were identified.
  
  
  CONCLUSIONS
  Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.
authors.affiliation: Hospital Universitari Germans Trias i Pujol and irsiCaixa Foundation, Ctra de Canyet s/n 08916, Barcelona, Catalonia, Spain. bclotet@irsicaixa.es
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bellos
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Goffard
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Andrej
authors.initials: A
authors.lastname: Wöhrmann
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilkin
authors.forename: Richard
authors.initials: R
authors.lastname: Haubrich
authors.forename: Calvin
authors.initials: C
authors.lastname: Cohen
authors.forename: Charles
authors.initials: C
authors.lastname: Farthing
authors.forename: Dushyantha
authors.initials: D
authors.lastname: Jayaweera
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
authors.forename: Peter
authors.initials: P
authors.lastname: Ruane
authors.forename: Sabrina
authors.initials: S
authors.lastname: Spinosa-Guzman
authors.forename: Eric
authors.initials: E
authors.lastname: Lefebvre
mesh_terms: D000328:Adult; D000069454:Darunavir; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood* / Q000187:drug effects; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir