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Genotype & Phenotype
Jun 22, 2002

Hey Doc:

I have three different friends who have taken Viracept and have all become resistent, with viral loads elevating in the presence of a compliant regimen. All three have gotten pheno and Genotype testing after becoming resistent to find that they were resistent specifically to those meds. (All normal so far). Now a year later when deciding what to go on this test was taken again and all three times (done three times because of the alarming results) they are now NOT resistent to Nelfinavir). This seems to be more common than once thought from what I have seen, where people can develop a resistance and actually be able to go back on medications they once used. All three are now undetectable on meds they have already taken before and were elevated in viral load for a full year on those same medications, riding them out sa long as possible.. I hope to get an answer to this question although something tells me I will not!



Response from Dr. Little

Actually, it is very common for people to develop resistance to drugs they are taking at the presnt time - and then after stopping those drugs - appear to develop drug sensitive virus again. In fact, the resistant virus persists, but generally in such a low amount that it is missed by the available genotype and phenotype tests which detect the predominant type of virus in the blood at the time of testing.

In general, if you reuse a drug that previous resistance tests showed drug resistance to that specific drug - then reuse of this same drug is not likely to promote durable suppression of virus. It is frequently possible to get the viral load below the limit of detection using the old (i.e. resitant drug), by adding additional more potent drugs - but I am always very cautious, since the resistant variant will often re-emerge and then the individual will fail the new regimen. The durability of the suppression may be shorter.

This does not mean that we never advise re-using drugs for which previous resistance tests indicated complete or partial drug resistance - there are circumstances where this is reasonable. It is not true though that just because the resistance test does not identify the persistance of a previously detected drug resistant virus, that it is now gone. It is much more likely that the amount of this drug resistant virus has dropped below the limits of the sensitivity of the assay, after discontinuation of the antiretroviral drug, and it is still there and more likely to re-emerge if the drug in question is restarted.

speed of resistance development
Adje clement, M.D.

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