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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Characterization of virologic failure patients on darunavir/ritonavir in treatment-experienced patients

Sandra De Meyer1, Erkki Lathouwers, Inge Dierynck

  • 1Tibotec BVBA, Mechelen, Belgium bJanssen-Cilag BV, Amsterdam, The Netherlands. sdmeyer@its.jnj.com

AIDS (London, England)
|May 29, 2009
PubMed
Abstract

Insights

Darunavir/ritonavir (DRV/r) showed a lower virologic failure rate and less resistance development compared to lopinavir/ritonavir (LPV/r) in treatment-experienced HIV patients. This indicates DRV/r is less likely to cause cross-resistance to other protease inhibitors.

Area of Science:

  • HIV/AIDS research
  • Antiretroviral therapy
  • Virology

Background:

  • Treatment-experienced HIV-1 patients often face challenges with drug resistance.
  • Protease inhibitors (PIs) like darunavir (DRV) and lopinavir (LPV) are key components of antiretroviral therapy (ART).
  • Understanding resistance patterns is crucial for optimizing treatment strategies.

Purpose of the Study:

  • To characterize resistance development in patients experiencing virologic failure on DRV/r.
  • To compare resistance patterns between DRV/r and LPV/r in treatment-experienced, LPV-naive patients.
  • To evaluate the impact of DRV/r on cross-resistance to other PIs.

Main Methods:

  • The TITAN trial was a phase III, randomized, controlled, open-label study.
  • Compared DRV/r (600/100 mg BID) with LPV/r (400/100 mg BID) in HIV-1-infected, treatment-experienced, LPV-naive patients.
  • Virologic failure was defined as HIV-1 RNA < 400 copies/mL after week 16; genotyping and phenotyping were performed.

Main Results:

  • Virologic failure occurred in 10% of DRV/r patients versus 22% of LPV/r patients.
  • Fewer DRV/r patients developed PI mutations (6 vs. 20) or NNRTI resistance (4 vs. 15).
  • DRV/r failure was associated with less loss of susceptibility to PIs compared to LPV/r.

Conclusions:

  • DRV/r demonstrated a low virologic failure rate with limited resistance development in this population.
  • DRV/r use was less likely to lead to cross-resistance to other PIs compared to LPV/r.
  • These findings support the use of DRV/r in earlier treatment lines for improved long-term efficacy.

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