Week 96 efficacy, virology and safety of darunavir/r versus lopinavir/r in treatment-experienced patients in TITAN

• Published in: Current HIV research Vol. 10; no. 2; p. 171
• Main Authors: Bánhegyi, Dénes, Katlama, Christine, da Cunha, Clóvis Arns, Schneider, Stefan, Rachlis, Anita, Workman, Cassy, De Meyer, Sandra, Vandevoorde, Ann, Van De Casteele, Tom, Tomaka, Frank
• Format: Journal Article
• Language: English
• Published: Netherlands 01.03.2012
• Subjects: Adult; CD4 Lymphocyte Count; Darunavir; Drug Therapy, Combination - methods; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - therapeutic use; HIV-1 - isolation & purification; Humans; Logistic Models; Lopinavir - adverse effects; Lopinavir - therapeutic use; Male; Middle Aged; Ritonavir - adverse effects; Ritonavir - therapeutic use; RNA, Viral - analysis; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Viral Load
• ISSN: 1873-4251
• DOI: 10.2174/157016212799937218

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.