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Resistance test conflicts
Jun 3, 2007

In March of last year, I was diagnosed with HIV. I have never been on treatment. In May, my doctor gave me a virco antivirogram phenotype, which showed I had a highly multidrug resistant strain. I believe the initial infection was in the Dec-Jan time frame. 6 months later, I requested both a phenotype and genotype/virtual phenotype. These were from a different lab company. Both of these tests came back showing my virus responsive to all treatments. From what I've read, transmitted resistance is much slower to fade and should show up on resistance testing up to 2 years or more from infection.

I've tried to apply for various clinical trials, expanded access programs, etc. but I am always denied since I've never been on treatment. At each appointment I ask for treatment, and my doctor doesn't agree, and I end up going with his opinion.

Since I seem to be ineligible for clinical trials and new medications since I'm treatment naive, I am interested in trying a first line, even if it means it may not work for me. My first resistance test showed me resistant to all components of atripla. The next 2 resistance tests showed me responsive to all 3 components. My doctor disagrees with me on this, but from what I see, if the first test was right, I'm not really risking any added resistance by trying atripla if I continue to be closely monitored, and if it's wrong, then I should be responsive to it, and may not have any issues of resistance.

Could you please provide me with your opinion? Thanks so much for your time and help.

Response from Dr. Sherer

With the information you have provided, I can't answer your question. The best I can do is to talk about these findings and what they might mean, and make some suggestions for you to discuss with your doctor.

In the more complex cases, such as yours, this forum does not lend itself well to simple answers. I would need to have a great deal more information to be able to help with your specific case. In particular, the exact findings of the first phenotype - including the genotype findings - and the second genotype and phenotype combination 6 months later would be essential. It might be of use to know whether you have any ideas about the source of the virus you acquired, particularly if it were likely to have come from a known individual with HIV on treatment.

Next, it would be necessary to know your current and past viral load and CD4 cell counts to gauge their absolute values and the trends in the values over time. Clearly, your doctor does not feel that this information, along with your clinical status, justifies starting ART at this time, regardless of the choice of agents. This is somewhat reassuring, and it suggests that you have some time to consider the implications of the information you have provided in your question.

Althoughy you are right that transmitted mutations often will persist for months or even years, that is not always the case. From the history you have provided, I am concerned that significant resistance mutations were present in March of last year, and that your virus has now reverted to wild type. This does raise the possiblity that you have archived resistance mutations, e.g. to EFV, TDF, and FTC, the individual drug components of Atripla. In order to make judgments about the best regimen for you if and when you do start ART, the details of these tests are critical.

If your virus had partial or complete resistance to Atripla, there is some potential damage from a therapeutic trial, because mutations may continue to accumulate in the NRTI class that may limit further options.

My suggestion is that you take this email response to your concerns and return to your doctor to ensure that you understand what these tests actually showed, and that you understang what his or her understanding is of the implications for you if and when you start ART. Your questions are perfectly reasonable: What do these tests mean? And ff and when the time comes, what regimen or choices of regimens would you offer me?


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