I've read some places that genotypic and phenotypic resistance testing requires 1,000+ PCR before they can be accurate, yet it seems like I've read cases where you've recommended testing when other people on the site have indicated smaller viral loads. Are there special considerations that would allow a resistance test to be run at <1,000 copies? I'm interested because my viral load is 600 and I dread the development of potential critical mutations while waiting for the VL to become >1,000.

I'm glad to have an opportunity to address this question, as it is a common source of confusion.

First, there can be considerable variability in viral load results from one time point to another. Higher viral loads occur in patients with recent immunizations or with active viral infections, for example; lower results would be expected after the viral infection resolves, or the impact of the immunization wanes. Lower viral loads may result from a lowering of the absolute lymphocyte count (causing a lowering in the CD4 cells that are producing virus), e.g. as a result of bone marrow toxicity from sulfa medications. Thus I may recommend that a patient with a viral load of 600 or 800 undergo genotypic analysis because the next value may achieve the threshold allowing for sequencing to occur.

There is also considerable variability in the absolute value of a viral load simply due to laboratory variability. To take the example of your last viral load, i.e. 600 copies/ml. Your clinician would only regard your next viral load value to be a clinically significant change from this value if it is 3-fold (0.5 log) higher or lower than 600 copies/ml, i.e. < 200 copies or > 1800 copies; otherwise it will be considered as comparable to your last value (even if the number is actually higher, e.g. 1,200, or lower, e.g. 350 copies/ml).

Finally, there are numerous steps in the performance of a genotype that can go smoothly, or be associated with technical difficulties. Sometimes viral loads of 600 or 800 can be sequenced, whereas viral loads of 1200 or 1400 cannot.

In sum, you are thus close enough to the threshold to justify an attempt at sequencing at this point, if your institution and the reference laboratory will do it. In order to reduce the number of tests performed without viable results, some labs demand that the initial threshold be met, so as not to waste reagents and personnel time. And some clinics, for similar reasons, demand the same threshold before they will even send out a specimen. Your physician may be able to overcome such limitations, or they may not be iron clad rules.

As in most cases, I urge you to talk to your doctor about your question and these options.