Week 96 Efficacy, Virology and Safety of Darunavir/r Versus Lopinavir/r in Treatment-Experienced Patients in TITAN

Denes      Banhegyi; Christine      Katlama; Clovis      Arns da Cunha; Stefan      Schneider; Anita      Rachlis; Cassy      Workman; Sandra      De Meyer; Ann      Vandevoorde; Tom      Van De Casteele; Frank      Tomaka

doi:10.2174/157016212799937218

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-naïve, 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.

Keywords: Darunavir, HIV, lopinavir, TITAN, treatment-experienced, efficacy, virology, safety