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next drug regimen????
Aug 15, 2000

The results of a genotype showed that I am resistant to: azt, 3tc, crixivan, sustiva, and viracept. The test does indicate that I am still sensitive to fortovase and partially sensitive to ziagen (it would take 5 x the concentration of ziagen to work). Here's my question. My viral load is currently 15k; my current meds are ampr/sustiva, combivir and ziagen. My Dr. will be adding in abt378 at the end of the month. I'm concerned that if I become more resistant to my current meds by waiting, it will be more difficult for the abt378 to work. With very few options left do you think waiting a few more weeks is reason for concern?

Response from Dr. Cohen

Well -- here are the issues.

The more the virus grows in the presence of your current meds, the more it tries to make more mutations that will help it to ignore, or become resistant to, your current meds. And unfortunately, since our meds are related within a class, you may show resistance to a medication you never even took -- because some resistance patterns help HIV ignore more than one drug at a time.

However -- resistance can be partial -- not complete, for some of our drugs. For example, you mention a fivefold resistance to abacavir/ziagen. What this means is that while there is some degree of resistance to abacavir, there is still a good chance that this drug might still have some potency to offer -- since it has been shown that it requires more than eightfold resistance to completely ignore abacavir's effects. By the way, if you ordered a genotype, you usually just get information about which mutations are seen. It sounds like perhaps you ordered a test that also included a phenotype -- which is when we learn the fold elevation type information you included. In terms of ABT 378 -- we have learned that this agent still has some significant potency even in those with up to seven mutations in the protease gene -- more than seven there is less chance of that medication working fully.

Now -- one more issue. We have also learned that one key way to overcome partial resistance is by getting higher than usual drug levels. For example -- you are now on amprenavir. You are also on sustiva -- and unfortunately, sustiva lowers the concentration of amprenavir in the blood making it less potent that it would be at standard blood levels. And if you boost the level even higher -- it could be even more potent. The usual approach when combining amprenavir and sustiva has been to add some ritonavir/norvir -- usually at a dose of 100 or 200 mg twice a day. This allows the amprenavir to be more effective for you by getting the correct blood level.

So what about waiting for 378? Well, the lesson we have learned over these years is that just adding a single drug is rarely successful for the long term. It might be -- and sometimes we can't wait for a second drug. But if you can wait for a second new drug to add -- we have learned that there is more success in controlling HIV when we give at least two new meds. And there are some others coming -- perhaps next year. Like tenofovir, and T-20 -- and perhaps a few others. And just boosting the amprenavir with ritonavir might reestablish better control of your viral load and keep you OK for longer. Until next year when newer meds become more available. In your case however -- saquinavir/Fortovase could be used now if you needed to start the 378 -- perhaps at a dose of 1000 mg twice a day.

By the way -- you mention that your genotype showed resistance to Sustiva -- and yet you are still on it. It may be worth checking to see if that is worth maintaining since sometimes there can be such high level resistance to that class -- the nonnukes -- that there is little if any benefit left from those meds. And then your amprenavir level could be higher off the Sustiva.

Hope that helps.



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