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Ask the Experts about Drug Resistance and Staying Undetectable
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viral blip conundrum
Sep 14, 2008

Hello Dr. Sherer -

My treatment history in an nutshell is: Initial V.L. in the millions- cd4 44. Started Sustiva/Truvada - discontinued after 10 days due to psychotic reaction. Changed to Boosted Reyataz/ Truvada - VL fell to 400. Added Ziagen one year later in attempt to achieve undetectable. Three years later changed to Kaletra/ Truvada/ Isentress. Initial labs showed undetectable (FIRST EVER) VL and +200 gain in CD4 (631). Two months later VL 176, CD4 - same.

My lapses/ vices are: -late by 2 or so hours several times. -Smoke cigarettes (about 1/3 pack a day). - Drink wine 3-4 times a week.

Also of note is that I went from HIV neg. to advanced AIDS in less than 4 years indicating a virile strain.

Since I have never had a geno/phenotype all the decisions we've made have been based on instinct and knowledge base. My instinct now is to go back to the old regimen (Reyataz etc.) and wait for my VL to rise to the point where we can genotype. I would hate to lose raltegravir and lopinavir too!

What do you think?

Thanks you Dr. for being there for us. --LA

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   Response from Dr. Sherer

I think that this forum is limited in many ways, and the more complex a patient's case, the less helpful I am able to be. For patients with complex treatment histories that can't really be described in a nutshell - like yours - it is not possible to offer credible advice, because too much useful information is missing. So you and your doctor are the ones to assess all avaiable clinical information and make the next treatment decision.

Having said that, I can offer some observations and try to respond to your question with the available information.

First, your lapses don't sound like a major issue, if you have otherwise been fully adherent to your various regimens. Of course, I urge you with your doctor to review these lapses and try to make any changes that will reduce or eliminate any missed meds or any delays in taking your meds in a timely way.

I appreciate that your history contains an uncommon but serious side effect of efavirenz that too few patients are familiar with, i.e. psychosis. For this reason, I advise patients to remain in close contact during the first months of EFV (Sustiva, one of the drugs in the three drug combo Atripla). I also appreciate that you are able to characterize your virus as 'more virulent' by the time course of the infection, i.e. from new infection to CD4<100 in 4 years. These details are helpful, and I understand that they factor into your physician's relatively aggressive responses.

Among the key peices of missing information are the outcome of the intensification with Ziagen, and the reason for switching to the current regmimen containing raltegravir (Isentress), including the results of drug resistance tests. If you were part of a clinical trial ever during your course, there may be a laboratory that would have banked, frozen serum on which a resistance test could still be performed. You can ask your doctor whether this is possible as a means to recover useful information from an earlier period in your clinical history.

While it is encouraging to hear that you are a well informed patient who participates in his management, I would discourage you from forming 'instinctive' management plans, whatever that means to you, and to rely on your doctor's advice at this point in a complex treatment plan.

Finally, I would not be so quick to act on a single viral load of 176. It could be a blip. You and your doctor should just repeat the test and make your decision then. You can send the specimen for a genotype and/or phenotye - in this setting, I would advise doing both tests - in the hopes that, if the next value is 500 copies or more, the laboratory may be able to sequence the virus and produce a result.

The quick decisions that have been made in your case without the benefit of resistance testing have added some uncertainty to your current management. This is common enough in HIV management, and your doctor can best explain the choices that were available to you and him or her at the time of each new regimen, and the rationale for the choices that s/he made.

The possible action that you describe does have some merit, in that you had some success with that regimen for 3 years (I am guessing), followed by some degree of virologic failure (guessing again), so you might be able to learn about the degree of underlying resistance that you had with that regimen. On the other hand, you are currently on a different regimen with different drug resistance mutation selection pressures, and your real concern is whether or not you have failed THIS regimen. In my opinion, you would be better off staying on this regimen, repeating the lab tests now, and, if the VL is rising, obtaining a genotype and phenotype on this regimen. That would allow your doctor to see if one or more of the signature RAL mutations had occurred, as well as possible other mutations against truvada or kaletra.

I urge you to take these comments with you to your next doctor visit.



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