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Re: Dr. Young, hello
Dec 5, 2001

Dr Young: Thank you for replying to my last posting. In your reply you raised the issue of drug resistence. What is the primary root cause of resistence? Is it poor adherence or the bodys inability to maximize HIV drugs? Thank you again for consideration of my questions.

Response from Dr. Young

thanks for your comments.

There are several root causes of resistance. The principle issue is that the HIV replication process is error prone, thus, anytime that the virus is given the chance to replicate in the presence of a drug, there is a chance that by mere random error, that a drug-resistance mutation might be generated.

In this context, it is important, therefore to keep the HIV drug levels at their optimum (though what optimum really is varies from drug to drug, if we really know this at all). There are many things which govern what is optimal- clearly if one misses doses of medications (i.e., poor adherence), then there will be times when the drug levels are lower than desired. This is probably why the more doses are missed, the higher the liklihood of resistance and virologic failure. There are also individual to individual variations in the way that the body absorbs and excretes the drugs. The later effects are likely overcome by using higher drug doses or, in the case of protease inhibitors, by boosting with ritonavir (or delaviradine).

There has been recent speculation that the risk of resistance is also greatest when there is more virus present (i.e., when the viral load is high). This may be why there has been a relative paucity of resistance emerging from STI studies that involve relatively short-cycle treatments, like 1 week on and 1 week off (compared with treatments with longer off periods). In the short-cycle treatment, the viral load rarely becomes detectable before the treatment is restarted. Whether this is really the case needs to be studied further, but is a tantalizing possibility.

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