title: Week 96 efficacy, virology and safety of darunavir/r versus lopinavir/r in treatment-experienced patients in TITAN.
abstract: Long-term potent activity of antiretrovirals is essential for HIV-1-infected, treatment-experienced patients. TITAN (TMC114/r In Treatment-experienced pAtients Naive to lopinavir) compared Week-96 efficacy and safety of darunavir/ritonavir (DRV/r) versus lopinavir/ritonavir (LPV/r). Treatment-experienced, LPV-naive, HIV-1-infected patients were randomised to DRV/r 600/100 mg bid or LPV/r 400/100 mg bid plus optimised background regimen (≥ 2 NRTIs/NNRTIs). 595 patients were enrolled (mean baseline HIV-1 RNA: 4.30 log10 copies/mL; median CD4 count: 232 cells/mm3). At Week 96, more DRV/r than LPV/r patients achieved HIV-1 RNA < 400 copies/mL (66.8% versus 58.9% [intent-to-treat (ITT)/time-to-loss of virological response (TLOVR)], estimated difference 8.7%, 95% confidence interval [CI]: 0.7-16.7), demonstrating the primary endpoint of non-inferiority of DRV/r (p < 0.001); the difference in response was statistically significant (p = 0.034). For the secondary efficacy parameter (HIV-1 RNA < 50 copies/mL) at Week 96, response to DRV/r was 60.4% versus 55.2% for LPV/r (ITT-TLOVR), estimated difference 5.8%, 95% CI: -2.3-13.9. Virological failure (VF; HIV-1 RNA > 400 copies/mL) with DRV/r (13.8%) was nearly half that with LPV/r (25.6%). Discontinuations due to adverse events were 8.1% for both DRV/r and LPV/r. Treatment-related grade 2-4 diarrhoea was 8.1% (DRV/r) versus 15.2% (LPV/r). Increases in triglycerides and total cholesterol were less pronounced with DRV/r. At 96 weeks, noninferiority (HIV-1 RNA < 400 copies/mL) of DRV/r over LPV/r was maintained; the difference in response was statistically significant. VF rate and treatment-related grade 2-4 diarrhoea were lower with DRV/r versus LPV/r.
authors.affiliation: Szent László Hospital, Budapest, Hungary. denes.banhegyi@laszlokorhaz.hu
authors.forename: Dénes
authors.initials: D
authors.lastname: Bánhegyi
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Clóvis Arns
authors.initials: CA
authors.lastname: da Cunha
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneider
authors.forename: Anita
authors.initials: A
authors.lastname: Rachlis
authors.forename: Cassy
authors.initials: C
authors.lastname: Workman
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.forename: Ann
authors.initials: A
authors.lastname: Vandevoorde
authors.forename: Tom
authors.initials: T
authors.lastname: Van De Casteele
authors.forename: Frank
authors.initials: F
authors.lastname: Tomaka
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D004359:Drug Therapy, Combination / Q000379:methods; 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 / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D061466:Lopinavir / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D061466:Lopinavir; D019438:Ritonavir; D000069454:Darunavir