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Important Questions?
Mar 31, 2002

Goodmorning Dr. Cohen. Over the past 6 years we have witnessed some great achivements in the field of HIV/AIDS care, namely the advent of HAART. But it seems there is still a lot of work to be done in the field. Could you take the time to answer a few questions? 1. Do you think we will be able to in the relatively near future(5-10yrs)have treatments for HIV that will make having HIV essentially minor? Treatments that allow people near 100 managment of the virus permanently? Without side effects that would make thier use difficult. If so could you share what you think might bring this about? 2. One of the problems facing people with HIV/AIDS is the sad fact that resistance to these drugs can and does occur,mostly perhaps due to missed doses, we seem to need more and more drugs to fight the virus. What number or classes of drugs do you think would be need to allow a us to not have to worry about the possiblity of resistance. Is it possible to develop drugs with such high gentic barriers to resistance as to prevent it? Do you think we could develop say 10 or 12 combinations that would last for say 50 or more years? 3. Finally what is the status of the new drug TRAIL? When can we exspect to know more on this exciting drug that may help us purge the reservior where the virus hides from the current medications? Thank you for your time doctor and many best wishes to you for all you do with this site.

Response from Dr. Cohen

Good morning/evening back to you. Here are some thoughts to address your questions/comments -

1 - We appear already to have meds that can make HIV minor - at least for some. When HIV is controlled, it appears to be a minor event for many. And then the issue is what you said - the side effects of the meds needed to render HIV impotent, no longer important. And these side effects are clearly the next hurdle in treatment research. Since we have potent weapons. Learning how to safely use them, or the future ones yet to come, is the key to turning HIV from what it is to what we want - a virus that no longer threatens lives. Clearly we are doing better with meds and side effects - newer meds and newer ways to use them allow better understanding of how to minimize side effects. But clearly more research is needed - since the problems continue to vex us.

2. Resistance from HIV is clearly a problem as you note. And we work on it in several ways. One is to prevent it from happening. As you note - we can generalize by saying that a lot of the resistant HIV we face is from less than adequate dosing of meds. And so we work on this by making the meds easier to take to minimize the risk of missing. And supports to those taking meds. And the option, once HIV is controlled, to even build it brief rest periods, or interruptions, that make pill taking less onerous for those who find it so. And ultimately, better and safer meds. With fewer side effects.

But you add one important added feature - the genetic barrier to resistance in some meds. Clearly, some meds can lose potency after HIV makes just one change in its genetic structure. And these are the meds that we call having a low barrier to resistance. While other meds require several changes for HIV to become resistant - and this takes longer. Some meds, like the boosted protease inhibitor Kaletra, have become important options given the observation that those who started on Kaletra as a part of their first treatment combination, and don't maintain full suppression, don't see Kaletra resistance despite this partial rebound. Viread, or tenofovir, has a similar story so far. With minimal resistance occuring -- at least not yet.

And this is different that what happens after HIV grows in the presence of other meds, such as epivir/3tc - which is a great med except that HIV can easily create resistance - which sadly causes about 2/3rds of the potency to be lost. Not all of it -- but a lot can be lost. And this loss is one reason why we want to avoid resistance. It can also cause the loss of other meds you have not ever taken yet - called cross resistance. For example, resistance to Sustiva/Stocrin/Efavirenz can result in loss to Viramune/nevirapine as well. So in time, we hope to identify meds that are attractive in many ways, including having the possible highest barrier to resistance.

3 - as for the trial TRAIL I'll admit I don't know what this is or the new exciting drug you ask about - but I'll check around... since trials can have many names and it can be hard to remember them by these "popular" names... but as for purging reservoirs - I think the search goes on for how to best do this - since if we could do this successfully, it has dramatic implications for treatment...

hope that helps.



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