Dr. Sherer,

The combo I have been on for several years now seems to be faltering. Over the last year, my VL seems to rise about 100 per month. Some times it's lower, but it never goes to 1000. Since I was on a regimen prior to my current one, my dr. wants to do a resistance test before switching - but I haven't yet gotten to the VL level where that is possible. What should I do? My current regimen is Trizivr and Sustiva and before that, I was on Viracept, Epivir and zerit. When I switched off that regimen (it was also failing after several years), my dr. was also not able to run a resistance test. Thank you, Alex

Your doctor has the option to send your blood for a resistance test, even if the viral load is not above 1,000. Sometimes sequencing is possible at lower viral loads, e.g. 500 or 700 copies/ml. That is one option open to you both, and on some occassions it will yield a useful result. I would advise you to do so. It may be useful for your doctor to communicate directly with the reference lab of his or her choice to explore these options.

There are also some research virology laboratories that are preforming 'ultra-sensitive' resistance testing, in which case they can sequence the virus at much lower viral load levels, even down to < 10 copies/ml in some cases. I don't recommend that you pursue this option, as it is very unclear what to do with the results that are obtained. That is, if a single clone of a resistance mutation such as the K103N is found (which is one primary resistance mutation for Sustiva (efavirenz), it is unclear what the clinical implications of such a mutation would be; it is possible that that single clone would be controlled by the drugs other than efavirenz in your regimen, i.e. by the trizivir, and so would never lead to clinical resistance.

If you are unable to sequence your virus, you and your doctor may choose either to continue with your current regimen or to make the best choice for another regimen and make the switch.

The recent change in guidelines regarding treatment experienced patients might also offer some guidance here. Due to the availability of active new drugs in new classes, such as the integrase inhibitor raltegravir and the entry inhibitor miraviroc, as well as the presence of two approved third generation protease inhibitors - tipranavir and darunavir - the goals of treatment for people with virologic failure with two or more regimens is still full suppression of the virus to below detection.

You should talk to your doctor about these options as part of your consideration for your next action.

I can't make a recommendation for you, based on the incomplete history that you have given. I would need to know some other things, including your current CD4 cell count, and the results of the CD4 cell count and virus load over the past year and since you started ART, your adherence record, side effects with past regimens, and other factors. I do agree with you and your doctor that a full assessment of your current situation is warranted, and it may well be that a switch to another regimen is in your best interest, rather than continued ongoing low level viremia.

Please take your concern and this response and discuss them with your doctor at your next visit.