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Resistance testing
Jun 22, 2005

My doctor may run a resistance test due to my CD4 count. I started treatment in June 2004. My viral in May 2004 was 331,000, my CD4 was 100; in August 2004 viral was 527, CD4 was 267; October 2004 viral was 158, CD4 was 158; and in January 2005 viral was 425 and CD4 was 252. In June 2004 I was taking Emtriva, Viread and Sustiva. In December 2004, they switched to Sustiva and Truvada. Would this be a sign of resistance even though I have never missed any doses?

Thanks, Steve

Response from Dr. Sherer

Failure to fully suppress after 6-7 months, as in your case, is more common with higher baseline viral loads, as you had. (As this is an old question, you may want to update me and the readers on what happened after this email from March.) We know that the most durable suppression is achieved when the level falls all the way to <50, a level you approached in October, but never quite made.

Your 'switch' was actually just a simpler form of the same regimen, i.e. with co-formulated tenofovir (Viread) and emtricitabine (Emtriva) in the form of Truvada. So you have only been on one regimen, and you have many options open to you if in fact this represented slow, early virologic failure.

Your doctor probably told you that it would be difficult to obtain a genotype test with a viral load below 1,000, though occassionally lower amounts can be sequenced - so you may not have been able to answer the question you have asked. It is possible that the failure to suppress represented resistance, though I would have expected the next results in October and January 2005 to be substantially higher if you had resistance to one or more drugs in the regimen.

Unfortunately, it is possible to develop drug resistance, even in the face of perfect adherence. Its important for physicians to alert patients to this possibility, though it is very infrequent.

Even with full suppression in the plasma to < 50 copies, viral evoluation continues, both in the plasma and in sequestered sites like the central nervous system and the gonads. In the majority of cases, these viral clones - which may be resistant to one member of the regimen - are suppressed by the other active drugs. Sometimes - infrequently - this will lead to virologic failure and overgrowth of a resistant strain.

You have done the best that you could have done by maintaining such a fine record of adherence. By all means, keep it up! As I noted above, it may have been that extra time was needed for full suppression, i.e. 9 months or more.

I urge you to take your question and these considerations to your doctor. And let us know what happened.


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