Characterization of virologic failure patients on darunavir/ritonavir in treatment-experienced patients

AIDS. 2009 Sep 10;23(14):1829-40. doi: 10.1097/QAD.0b013e32832cbcec.


Objective: Characterization of resistance development in virologic failure patients on the protease inhibitor darunavir administered with low-dose ritonavir (DRV/r) in the 48-week analysis of TMC114/r In Treatment-experienced pAtients Naive to lopinavir (TITAN).

Design: TITAN is a randomized, controlled, open-label, phase III, noninferiority trial comparing the efficacy and safety of DRV/r with that of lopinavir/ritonavir (LPV/r) in HIV-1-infected, treatment-experienced, LPV-naive patients. The primary endpoint was the proportion of patients with HIV-1 RNA less than 400 copies/ml at week 48.

Methods: Patients received DRV/r 600/100 mg twice daily (n = 298) or LPV/r 400/100 mg twice daily (n = 297), and an optimized background regimen. Patients who lost or never achieved HIV-1 RNA less than 400 copies/ml after week 16 were considered virologic failure patients. Genotyping and phenotyping were performed.

Results: The virologic failure rate in the DRV/r arm (10%, n = 31) was lower than in the LPV/r arm (22%, n = 65). Furthermore, fewer virologic failure patients in the DRV/r arm than in the LPV/r arm developed primary protease inhibitor mutations (6 vs. 20) or nucleoside reverse transcriptase inhibitor resistance-associated mutations (4 vs. 15). In addition, fewer virologic failure patients on DRV/r than on LPV/r lost susceptibility to the protease inhibitor (3 vs. 13) or nucleoside reverse transcriptase inhibitor(s) (3 vs. 14) used in the treatment regimen or to other protease inhibitors. Most DRV/r-treated virologic failure patients retained susceptibility to all protease inhibitors.

Conclusion: In treatment-experienced, LPV-naive patients, the overall virologic failure rate in the DRV/r arm was low and was associated with limited resistance development. These findings showed that the use of DRV/r in earlier lines of treatment was less likely to lead to cross-resistance to other protease inhibitors compared with LPV/r.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • Darunavir
  • Drug Resistance, Multiple, Viral / genetics
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Lopinavir
  • Mutation
  • Pyrimidinones / therapeutic use
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Ritonavir / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Treatment Failure
  • Viral Load


  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Pyrimidinones
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Sulfonamides
  • Lopinavir
  • Ritonavir
  • Darunavir