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Abstract
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)
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
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.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
Abstract no.
TUAB101
Suggested Citation
"Valdez-MadrugaJ., et al.
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).
Oral abstract session:
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention:
Abstract no.
TUAB101"
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