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Resistance test requirements
Dec 8, 2007

I am about to take a Virtual phenotype/genotype resistance test named VIRCO.My doctor and I want to change meds since I could not tolerate the last HAART based on Kaletra+Trizivir I was found to be resistant to NNTI and 3tc in 2003. Last VL 38.000 CD4L 290. I`ve been out ot meds for the last 2 years. This is my specific question: Is it mandatory/essential to be under HAART to perform such a resistance test? Will the results be reliable if I am not taking any antiretroviral drug? Thanks for your time. Regards, Sebastian.

Response from Dr. Sherer

It is far more useful to perform a resistance test while you are taking an ART regimen than when the patient has been off medication, as in your case.

While you are taking your medication, a resistance test will give specific information about the presence or absence of resistance to the drugs in that regimen.

After a person on ART stops their drugs, wild type virus overwhelms the virus clones with drug resistance, and most resistance test results will show 'wild type' virus, because indeed the wild type virus will be the majority population in the swarm. This will generally occur promptly in the first month after cessation of ART. However, that does not mean that you would then be susceptible to all drugs, as if you really had a wild type virus, due to the phenomenon of 'archived resistance', meaning that you still have minority clones of virus that contain all of your previous drug-resistance .

For this reason, a resistance test while off medications is less useful than one obtained while you are still on medications. The test is equally reliable in all settings, but it is less valuable because of the phenomenon of reversion to wild type virus.

It should also be said that some resistance mutations, for example NNRTI resistance mutations, may persist long past the usual 2-6 week period during which most mutant virus will be overwhelmed by an overgrowth of wild type virus. In a minority of patients, NNRTI mutations will persist for 6-12 months or more, and these mutations may show up on a genotype performed 6-12 months after cessation of an NNRTI-containing regimen.

These realities allow you and your doctor a few options. Had you tolerated your previous regimen, you and your doctor could choose to simply resume your previous regimen and perform a resistance test after 1-2 months to determine your drug resistance pattern to this regimen.

However, since in this case you were intolerant to that regimen, it would be more reasonable for your and your doctor to choose an alternative regimen and then perform a resistance test if and when you show evidence of virologic failure, or failure to reach a viral load below the level of detection.

You should be able to find a satisfactory altnerative regimen with good virologic and immunologic outcomes. I urge you to share this email, these responses, and your concerns with your doctor at your next visit.


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