[Darunavir as first-line therapy. The TITAN study].
Lopinavir/ritonavir (LPV/r) has been the gold standard in first line rescue treatment for many years. No other boosted protease inhibitor (PI/r) has managed to demonstrate that it is superior to LPV/r. In this regard, the TITAN study compared the efficacy and safety of darunavir (DRV/r) in 595 patients, at a dose of 600/100 mg two times a day against the normal LPV/r dose, combined with at least 2 other optimised antiretroviral drugs. The efficacy of the treatment at 48 weeks (VL<400 copies/mL) was significantly higher in the DRV/r goup compared to the LPV/r group, both in the analysis by protocol (77% vs. 68%), the non-inferiority of DRV/r being demonstrated (estimated difference +9%, 95% CI 2-16), and by intention to treat (77% vs. 67%), the superiority of DRV/r being demonstrated (estimated difference 10%, 95% CI 2-17%). The incidence of diarrhoea and increase in triglycerides was higher in the LPV/r group. The differences in efficacy of both treatments in favour of DRV/r started to be seen from a basal primary mutation in the protease, with these differences increasing as the number of these mutations increased. In patients with virological failure, DRV/r protected the protease and reverse transcriptase against mutations, thus preserving future therapeutic options. We have some theoretical and clinical data available that enables us to consider the possibility of administering DRV/r once a day in some patients with a few mutations in the protease and in those where this dosing regime is considered important. With the results of the TITAN study, DRV/r must be considered the new gold standard in first line rescue, at least in those patients with a primary mutation in the protease.
Curran
Adrian
A
Servicio de Enfermedades Infecciosas. Hospital Universitario Vall d'Hebron. Barcelona. España.
Ribera Pascuet
Esteve
E
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D000069454:Darunavir; D003967:Diarrhea / Q000139:chemically induced; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced; D061466:Lopinavir; D008297:Male; D011379:Prognosis; D011744:Pyrimidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D016879:Salvage Therapy; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D061466:Lopinavir; D019438:Ritonavir; D000069454:Darunavir