Aug 1, 2009
Hi Dr. i am a pharmacy professional working in ART clinic in ethiopia. i need to now if there are any updates with related to resistance and the basic mechanism for hoe the PI groups will make resistance.additionaly can you tell me about codons? thank you.
Response from Dr. Sherer
I am happy to refer you to several excellent web sites that deal more comprehensively with the mechanisms of resistance, and with ongoing research into resistance to ARTs, than this site.
First, I suggest the IAS-USA Drug Resistance Mutationa Group website at www.ias-usa.org. This group publishes annual updates to their guidelines for resistance to HIV-1. You can find the guidelines at Hirsch MS et al, Clin Infect Dis 2008;47:266-288.
For the clinical application of resistance information, I recommend the DHHS Guidelines at this website: http://AIDSinfo.nih.gov.
Another useful source of information on HIV drug resistance mutations is the Stanford University HIV Drug Resistance Database, at http://hivdb.stanford.edu.
In general, aspartyl protease inhibitors require multiple single mutations in and around the active pocket of the enzyme at key mutation sites, such as the 10, 46, 54, 73, 82, 84, and 90. Also in general, the risk of phenotypic mutations increases with a rising number of these mutations. Some PIs have sentinel mutations that arise early and are associated with significant reduction in activity, such as the D30N in nelfinavir. In many cases, specific clusters of mutations are associated with a greater reduction in susceptibility for individual drugs. I refer you to the above references for greater detail on these points, and for more discussion of the role of codons in drug resistance.
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