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Unable to genotype or phenotype
Jul 4, 2005

I have been positve for 13 years with almost no complications and have usually been undetectable or close to it after starting meds 7 years ago. Recently my viral load has climbed into the into the 1500 range. My doctor has had two genotypes run and a phenotype from two different labs and each time they are unable to determine the mutation. My doctor is recommending switching from Viramune/Viread/Trizivir to Sustiva/Videx/Truvada. I had been on this regimen for almost the entire time with the exception of Viread which was added recently when my viral load started to climb. I am concerned that about not having a clear indication as to which direction to move towards. How common is it not to be able obtain the results on these types of test? What are the implications of moving to the new meds in regard to further resistance. I guess after all this time of having good years, I am concerned about the change. Thanks for your help.

Response from Dr. Sherer

Although clinician's are advised that genotypes may be difficult to obtain at viral loads below 1,000 with standard assays, the ability to obtain a genotype sequence is not only determined by the amount of circulating RNA in the blood. Other factors can include other genetic material in the blood that might mimic HIV RNA and confuse the assay, the sensitivity of the assay itself, the integrity of the reagents used to amplify the RNA particles, intereference in the assay caused by high triglycerides or bilirubin, and other factors. Inability to sequence a virus when the viral load exceeds 1,000 occurs often enough, as often as 10-20% of the time.

You and your physician are faced with the difficult options of waiting while you take your current regimen until a genotype can be obtained, i.e. with yet another (third) attempt, or making your best judgment about possible alternative regimens without the information from a genotype and making a switch. You didn't note the amount of time that has passed since you developed viremia of 1,500 copies/ml and started trying to get a genotype; it is likely to be 2 months or more.

It would be useful to know the duration of time since the first viral load over 1,000, and the number of tests at that level or higher, in making this judgment. Also, you have not noted your adherence to ART, though your past good performance suggests that it has been very good. We know that even patients with perfect adherence for many years can suffer from 'pill fatigue' and lapse into less than perfect adherence. I would want to review your recent adherence at a minimum before making a switch to new one.

The risk of continuing on your current regimen while viremic is the development of additional mutations, particularly to the NRTI class and to Viramune (nevirapine). The risk of switching without this information is that the second line regimen may include drugs to which you are fully or partially resistant, which would also promote new resistance mutations.

Finally, the second line regimen that has been proposed - Sustiva (efavirenz) + Videx (didanosine) + Truvada (emtricitabine or FTC + Viread or tenofovir) contains only one drug with a somewhat different NRTI resistance profile, i.e. didanosine.

Without all of the needed information, I can't help you any more than offering the above considerations. On the basis of what you have said, I lean towards obtaining a third genotype while you remain on your current regimen. More important that this opinion would be to review all of these thoughts with your doctor, and make your plans for the next steps with him or her.


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