title: Second generation HIV protease inhibitors against resistant virus.
abstract: BACKGROUND
  The AIDS epidemic has spread around the world at an alarming rate. Although the first generation of HIV protease inhibitors, including indinavir, nelfinavir, saquinavir, ritonavir and amprenavir, were initially effective against HIV infection, the fast emerging resistance to these agents has been a substantial and persistent problem in the treatment of AIDS. Attempts to address the resistance issue with 'salvage therapy' consisting of high doses of multiple protease inhibitors have only been moderately successful owing to the high level of cross-resistance and toxicities associated with the protease inhibitors.
  
  
  OBJECTIVE
  To study the second generation HIV protease inhibitors against resistant virus.
  
  
  METHODS
  This review highlights new developments achieved by various organizations to address the challenge of high level resistance of current therapies since 2000.
  
  
  CONCLUSIONS
  All second generation protease inhibitors used in patients who experienced extensive treatment require ritonavir as a pharmacological boosting agent to increase the drug level in the plasma, but there is toxicity associated with such a practice. Accordingly, there remains a need for new protease inhibitors with improved effectiveness against the resistant viral variants. A third generation protease inhibitor will require no boosting agent while maintaining high potency against resistant virus.
authors.affiliation: Merck & Co., Inc., Merck Research Laboratories, Department of Medicinal Chemistry, R800-C307, PO Box 2000, Rahway, NJ 08809, USA +1 732 594 4392 ; +1 732 594 9473 ; Zhijian_lu@merck.com.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Lu