To: Elroy Jetson who wrote (114 ) 8/15/2009 5:47:03 AM From: idos Read Replies (1) | Respond to Development of resistant isolates depends on mutations to acquire resistance. Time to these mutations largely depends on selection pressures. The harder the selection pressure is, the quicker mutations will occur. A drug with low antiviral activity does not exert substantial selection pressure on the virus, and the virus does not need to adapt rapidly, so chance of drug resistance is not very high. Conversely, complete suppression of viral replication allows little opportunity for resistance to emerge because mutagenesis is replication dependent. So, a more potent drug is not necessarily the one with the better resistance profile. Increased number of mutations needed for resistance will make the development of resistance slower. There are unique mutations to each agent: S153Y is selected by raltegravir, and Q148K and T66I are elvitegravir-associated mutations. Some specific mutations, called “primary,” are able to confer very high fold changes or resistance and it is assumed by researchers that two mutations (a primary and a secondary) are generally required for resistance, but the second mutation usually follows very quickly behind the occurrence of the primary. It is not yet clear if elvitegravir resistance requires more or less mutations than raltegravir and suggesting one of them has a higher barrier to resistance is premature. That is why I didn't highlight this sentence which you choose to ignore from the abstract:"Both drugs exhibited a parallel resistance profile, although resistance was generally greater for elvitegravir."
