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Resistant to all meds
Dec 8, 2003

Hi:

I have been HIV+ since at least 1981 but never got sick. However, I have shown resistance to everything and my viral load ranges from 40,000 to 80,000. My t cell count ranges from 290 - 450. My doctor has me on kaletra, norvir, viread, rescriptor, trizavir, wellbutrin, neurontin, gemfibrozil, and acyclovir. I seem to be doing fine and feel good. I have been on this regimen for about two years. He does not want to change anything until at least two new meds become available. I trust him but am concerned with all the meds I am on and the fact that I am also on testosterone, deca durabolin, and ritalin. My cholesterol is ok but my trycliceride level is 1200. Does this make sense or is it bad that I am taking so many meds which all show resistance. He says that the meds keep the new virus down and that the virus that is showing activity is old and mutated and not as dangerous. I need another point of view.

Thank you.

Response from Dr. Cohen

This is a common and difficult circumstance. There however clearly are many who face these issues. So here are some observations.

While we go for full viral suppression whenever possible, there are many who can't achieve this goal due to accumulated resistance and a lack of new agents to get full control of this virus. Fortunately we have new meds in development. Unfortunately they come to be FDA approved at a slow rate and for some this means waiting. For example there is now a drug called enfuvirtide or Fuzeon. And this single drug is likely to be new and potent for almost all in this circumstance. And as a result there is ongoing discussion and debate about when to use this new drug do we use it now, or do we hold and await a second new drug to come thru. And if that is the case waiting for another new drug -- it might be a while. Since another drug that is active against resistant strains of HIV might take a year or more to arrive. So what to do?

Well, resistance testing can often assess what activity might be left in the approved drugs. Based on what you've written, it is unlikely that any other available agent will have a high degree of predicted activity, but sometimes, especially with the protease inhibitors, we have surprises. So some would assess this, and if there is another drug to add to the enfuvirtide, these two new agents might be options. The combination of enfuvirtide plus even just one more active drug has been successful at reestablishing full suppression in about 1/3 of people who have used it this way... and there's a longer article on theBody web site that goes into more details about this.

So if that is not the case there are no active drugs to add -- then what? Well, another key issue is whether ANY of your current medications are active. And the easiest way to know if that is the case is to ask what your highest viral load has ever been in the past. Since if for example it was 250,000 in the past, and is now about 50 thousand then at least some of the current meds are partially active. Narrowing down your current combination to the ones that deserve the "credit" for this partial suppression is another potential use of resistance testing but sometimes we cannot fully explain what accounts for this outcome. And that's because of one other observation.

We've learned that sometimes HIV pays a price to become resistant to some medications. It is less "fit" or less able to grow because of the mutations that it has created in order to become resistant to our antivirals. There is a test that tries to capture this called a "replicative capacity". But with or without this test the only way to really know if your meds are even partially active is to know if your current viral load is lower than it would be off meds. And we don't have a test quite that accurate. But we do know that, for example, a virus with the M184V mutation is reliably less fit than the wild type - by about a half-log - and this prompts most of us to include a drug that maintains this mutation in any combination where we are striving for at least partial control. Drugs like epivir and the newer agents Emtriva are reliable at selecting for this mutation...

Now, this does NOT necessarily mean you should stop meds to see what your viral load would be off these meds. Some, especially those with a very low CD4 count in the past, can have significant drops in their counts when they stop all antivirals. But if your counts were never below, say 150, some have explored stopping all antivirals as a way to limit the ability of HIV to create even more resistance to our meds, which unfortunately might undermine the activity of the very meds you are waiting to use in the future (more resistance, more cross-resistance) -- as well as noting that time off meds can obviously decrease drug toxicity. This approach is being explored in a study that you can read about on line (www.smart-trial.org).

And at least one researcher has explored stopping just some of the meds in a combination for example, he found that for some people, one class of drugs (NRTIs) accounted for much of the activity of the combination, and allowed people to have weeks to months off at least some of the meds while maintaining a similar viral load. There's less info about this but this is another way to explore what to do next.

As you can see there is much going on here and much uncertainty about the best way to go. But the overall message is that partial suppression can often preserve CD4 counts sometimes for months, and sometimes longer. Even if it means putting up with some short term side effects.

Oh yeah - there may be options given the triglyceride elevation you note. This is likely due to the Kaletra and Norvir - you may not have to treat the triglycerides - but if you and your clinician think it is important to do so - options include one of the newer PIs that have become available in the past year especially atazanavir or maybe fos-amprenavir in case they have something to offer to you. Or adding a statin - like Lipitor - since it might lower the trigs further...

Sum: if you have a combination that is partially working and especially if you have a history of low CD4 counts in the past maintaining you on some antivirals is our current standard approach to keeping you well. While you await the second new drug to get here and then make good use of the enfuvirtide that's sitting there...



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