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MDR! Still take meds?
Feb 18, 2007

Dear Dr Sherer

Obviously drug resistance has become a huge issue in the HAART era. Having read many question in this wonderful site many times, I have a few questions that I have a burning desire to know the answers to.

1.Treatment or no Treatment? If people develop resistance to all classes of drugs but can still tolerate the medications without massive toxicity, should they stop taking meds and wait for expanded access to new ones? Or is it still better to take the drugs that the HIV has developed resistance to? Does treatment still have any effect on multi drug resistant HIV at all?

2.Viral Fitness? I have heard that while HIV mutates it looses some of its Viral Fitness. Do you believe it would ever be possible to cripple HIVs viral fitness to such an extent as to significantly reduce its ability to fight the immune system and cause death to the person?

3.Resistance Reversal? Is drug resistance ever reversible? Can other HIV meds or just stopping that particular class of drug for many years reverse drug resistance mutations?

Thank you very much for your time, I would be very grateful to you if you answer these questions. While I am frightened by what the future of HIV treatment holds, am also fascinated by the advances being made, they help me maintain an optimistic outlook. People like you make this happen, and websites like this help inform those who are desperate to know the up to date news.

Thank you very much

Response from Dr. Sherer

The evidence is clear that a person is better taking ART than NOT taking ART, even in the presence of resistance to many or all drugs.

The benefits include lower mortality and lower risk of new AIDS opportunistic infections.

There are several reasons. First, even ART medications to which the virus is partially resistant may still have some antiviral activity, and so may make an important contribution in a three drug regimen.

Another reason is the reduced fitness of the virus caused by mutations to some ART drugs, particularly the nucleosides like 3TC (lamivudine) and some protease inhibitors. The mutations that these drugs cause appear to impair the ability of the virus to replicate and cause morbidity and mortality. In several studies comparing stopping all drugs to maintaining some or all drugs in a regimen to which a person is resistant to, the clear advantage goes to those who continue to take ART. Your caveat was important as well, i.e. this is the best strategy when the drugs are relatively well tolerated.

Some resistance can be overcome, e.g. by increasing the plasma level of the drug, but it is best to think of resistance as 'permanent'. However, the HIV virus is unforgiving, and once it has been given the upper hand -- for example when a person on Sustiva misses many doses over a few weeks, and resistance to Sustiva develops -- the virus will never lose that resistance, and the mutation will become 'archived', so that even if the same patient takes Sustiva after 5 years on another type of therapy, the virus will retain the ability to become fully resistant rapidly to Sustiva.

I urge you to take these general comments to your doctor and talk about your specific concerns and situation with him or her, as the answers may differ somewhat, depending on your current and past treatments and your response(s) to them.


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