 |
Comparison of 48-week efficacy and safety of darunavir/ritonavir (DRV/r) with lopinavir/ritonavir (LPV/r) in LPV/r-naïve, treatment-experienced patients: a randomised, controlled phase III trial (TITAN)
Presented by Jose Valdez-Madruga, Brazil.
Valdez-Madruga J.1, Berger D.S.2, McMurchie M.3, Suter F.4, Banhegyi D.5, Ruxrungtham K.6, Lefebvre E.7, De Paepe E.8, Tomaka F.9, De Pauw M.8, Vangeneugden T.8, Spinosa-Guzman S.8
1Centro de Referência e Treinamento DST/AIDS, São Paulo, Brazil, 2Northstar Medical Center, Chicago, IL, United States, 3University of Sydney, Sydney, Australia, 4Ospedali Riuniti di Bergamo, Bergamo, Italy, 5Szent Lásló Hospital, Budapest, Hungary, 6Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 7Janssen-Cilag, Tilburg, Netherlands, 8Tibotec BVBA, Mechelen, Belgium, 9Tibotec Inc, Yardley, PA, United States
Objectives: To compare long-term efficacy and safety of DRV/r vs LPV/r in a randomised, controlled, phase III trial (TITAN) in patients with limited treatment experience.
Methods: Treatment-experienced, LPV-naive, HIV-1-infected patients (VL >1,000copies/mL) on stable HAART or off-treatment for ³12wks were randomised to receive DRV/r 600mg/100mg bid or LPV/r 400mg/100mg bid plus OBR (³2 NRTIs/NNRTIs). Primary endpoint was non-inferiority (delta of 12%) in confirmed virological response (VL <400copies/mL, TLOVR) at 48wks. In case of non-inferiority, DRV/r superiority was a secondary endpoint.
Results: 595 patients enrolled (79% male; mean age 41y; mean baseline VL 4.30 log10copies/mL; median CD4 232cells/mm3); overall, 31.4% were PI-naïve; 81.8% had susceptibility to ³4 PIs (baseline Antivirogram®). At 48wks, significantly more DRV/r than LPV/r patients achieved VL <400 and <50copies/mL (Table). The lower limit of the 95%CI for the difference in response between DRV/r and LPV/r did not exceed −12%, establishing non-inferiority, and did not include 0, thereby confirming superiority of DRV/r over LPV/r (p=0.008). Most common (>12%) AEs with DRV/r were diarrhoea (31.9%), nausea (18.5%) and nasopharyngitis (12.4%), which occurred in 41.8%, 20.9% and 11.1% of LPV/r patients, respectively. Discontinuations due to AEs were low (0.7% for rash in the DRV/r arm).
| Week 48 parameter | DRV/r bid + OBR (n=298) | LPV/r bid + OBR (n=297) | Estimated difference between DRV/r and LPV/r | | VL <400 copies/mL (TLOVR), n (%) | 228 (77%) | 199 (67%) | 10% [2%; 16%]* | | VL <50 copies/mL (TLOVR), n (%) | 211 (71%) | 179 (60%) | 11% [3%; 19%]* | | Mean (±SD) log10 VL change from baseline (NC=F) | −1.95±1.24 | −1.72±1.34 | −0.20 [−0.39; −0.004]* | | Median CD4 increase, cells/mm3 (LOCF) | 97 | 102 | | | Incidence of serious AEs / patient discontinuations due to AEs (%) | 9.4% / 6.7% | 10.4% / 7.1% | | | Grade 3 or 4 lab abnormalities for total cholesterol / triglycerides (%) | 8.3% / 9.0% | 10.7% / 14.5% | |
Conclusions: In this trial evaluating LPV/r-naïve patients with limited treatment experience, the primary endpoint was reached and treatment with DRV/r was generally well tolerated and proved superior to LPV/r in virological response.
Back to the session -
Back to the Programme-at-a-Glance
|
|