Surrogacy in antiviral drug development.
The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therapeutic intervention have started to give way to the use of an increasing number of surrogate markers. Using a combination of these markers, it is now possible to measure and monitor the pathogen as well as the host's response. Nowhere is this better exemplified in virology than in the field of AIDS. We have utilized the advances in pathogenesis and new antiretroviral drug development to: * develop a new class of drugs which block the entry of HIV-1 into cells. * develop a new approach for effectively delivering these drugs to those tissues in which most viral replication takes place. Over the last 10 years, our work has progressed from concept to clinical trial. Our laboratory based evaluation of the new molecules developed as well as our clinical evaluation of their safety and efficacy have had to respond and adapt to the rapid changes taking place in AIDS research. This paper discusses the problems encountered and the lessons learnt.
Shaunak
Sunil
S
Faculty of Medicine, Imperial College at Hammersmith Hospital, London W12. S.Shaunak@ic.ac.uk
Davies
Donald S
DS
D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers / Q000032:analysis; D018925:Chemokines / Q000502:physiology; D003912:Dextrins / Q000627:therapeutic use; D004197:Disease Reservoirs; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D011134:Polysaccharides / Q000627:therapeutic use; D018121:Receptors, Cytokine / Q000502:physiology; D014779:Virus Replication
D015415:Biomarkers; D018925:Chemokines; D003912:Dextrins; D011134:Polysaccharides; D018121:Receptors, Cytokine; C091377:dextrin 2-sulfate