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HIV Drug ResistanceHIV Drug Resistance
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Oct 9, 2006

I was diagnosed in 1991 and took AZT monotherapy for nearly two years. I have taken most of the drugs available and I have never been undetaectable. i took T-20 from 2001 and had to stop as it had also failed but was told I could not use Tepranavir so I was taking D4t, tenoforvir, Fosamprenavir, Sequinavir, 3TC Retonovir, and T-20. A year ago I was put on a combination of TMC 114 and TMC 125 but I stopped taking the T-20 due to running out of injecting sights. I have developed resistance yet again and my CD4 is 31, viral load is 84,000 at the moment. I have reccurring thrush in the mouth and viginal thrush from time to time. My Dr. is also comfussed at how my virus keeps defeating all I have thrown at it. Have you got any suggestions as to how I can beat this awful situation?

Response from Dr. Sherer

This is a very distressing story, and yet this should be a year in which there is still some hope for another active regimen for you.

It will not be possible for me to consider all of the issues in your care, as people with extensive past treatment histories, and unique, complex resistance patterns require the greatest amount of accurate clinical information in order to make the best recommendations, and the internet is not the best way to achieve that. I will make some observations, and ask that you share them with your doctor. I will say that your doctor has shown considerable initiative already by getting you into the trial of two new drugs, i.e. TMC 114, now FDA approved as darunavir (Prezista), and TMC 125, the new NNRTI that is available via expanded access, and is active against most NNRTI-resistant virus.

My first suggestion is for your and your doctor to explore the various ways to treat thrush. Are you already on high doses of fluconazole? Have you tried other imidazoles as well? For some patients, intermittent IV amphotericin works best to control the infection, and is worth the try.

The next suggestion is for you and your doctor to review all of the resistance data again, including the most recent resistance tests, to be sure that darunavir and TMC-114, as well as the current NRTIs such as tenofovir and abacavir, are no longer active.

Next, you and your doctor should consider whether you should resume T-20 (enfurvitide), since there is some evidence that it has activity even when you have used if for a long time and some degree of resistance has occurred.

Next, you and your doctor can explore accessing new drugs in two classes, i.e. an oral entry (miraviroc), which is soon to be available by expanded access. Your doctor will need to perform a blood test to determine whether you have CCR5 tropic virus, which is most common, or CXCR4/CCR5 mixed virus, which increases from 20% to 40-50% in patients with CD4 cells below 100 cells/ml, as your are. (Even if you have the X4 virus, a trial of miraviroc is warranted, because in a recent trial, no harm occured to patients with X4 virus who received the drug, and the CD4 cells increased.)

And finally, the first integrase inhibitor MK0518 will soon be available by expanded access, and you and your doctor can explore accessing this drug when it becomes available. It appears to have good tolerability and potent activity in early clinical trials.

FInally, you and your doctor should formulate a plan to last until these new drugs are available. There is good evidence that some ART is better than none, so I would not recommend a drug holiday.

As above, please take your questions and these observations and share them with your doctor.

Why am I not undetectable yet?

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