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just give an estimate already!
Oct 26, 2002

ok, please, stop being too cool to give an opinion. how many years do YOU THINK until there are therapies for hiv that have little to no toxicity and are successful at keeping viral loads undetectible without short or long-term side effects? be it antiretrovirals, imune based, whatever. tell me what direction you think we're moving in, and what you see in the how near future.

Response from Dr. Cohen

Well, that's quite a compliment you've got going in that opening sentence - but Ok. You got me. I admit it. I've been way too cool I guess. Probably comes from a particularly rough Junior High School experience... But, I've never considered that minimizing personal opinion and instead presenting the facts as I see 'em as too cool. But since you've asked... here's my take on the issues.

We do know some who have HIV can keep HIV under control - the immune system is rarely that good but when it is - it does keep HIV well controlled without apparent illness for years and years... and so it is a focussed search for things that can replicate this success. Within the immune-based world - the closest we've come so far is very early recognition and treatment and then some mix of stops and starts to recreate this outcome. Or so it seems at this early stage. But - for those who are facing seroconversions from HIV - it is critical to at least consider getting into the hands of someone expert in treatment - since our cellular immune system may get one solid chance at that successful outcome - and time is the enemy. And there are a few study sites leading the way in this - including one collaboration here in Boston and others elsewhere. As for immune based treatment after this point - the search continues with hints of possibles but nothing yet substantial enough to consider proven. But more work does continue as the hints are at least present that we might recreate this success some of the time...

And what about meds when it is too late for early recognition? Well, we already at least one med that meet your threshold. We've got others that work well with little expected toxicity and are successful at keeping HIV under control. Probably the incontrovertible leader in the field of meds for now is Epivir - called 3TC or lamivudine. This one pill is the most frequently prescribed med we've got in the field. And it earns that rank due to a seemingly negligible toxicity profile. If there truly are side effects from this med - they're rare events. And when used for the first time against a strain of HIV that is sensitive to it - it can drop the viral load about 1.5 log -which is pretty potent. But, its Achilles is that HIV just needs one change in its genetic structure to learn how to grow despite it - and then we lose about 2/3 of the potency from this one drug. But in effective combinations this doesn't happen - so we have at least one solid card in the deck.

Indeed - we have no single med yet proven powerful enough on its own to control HIV - so we'll need more than one for now - until we find that single potent agent.

A second potential for this category may be the new drug tenofovir or Viread. It too is simple, and free for most people of subjective toxicity and while it is too soon to be confident about the 5 year tox patterns - so far it is looking favorable. As with epivir, it is potent against wild type virus. As similarly can lose potency after resistance can occur from other related meds. But is an attractive drug to have around.

And that is just the beginning of the list. Others on the list are often well tolerated by many - even if some do have toxicity, others don't. And that matching of people to the right drug is the challenge we have - but when we get it right, we can and DO often meet your goals. And since any drug might have subtle long term toxicities, there is research going on about switching and changing and even interrupting to minimize the side effects while maintaining their efficacy and benefits. But we've got enough choices so that for some getting started, there's a good chance to have a coupla combinations that do well for most.

As for the future. I can only say that companies are only gonna commit their considerable resources to new drugs if they offer some advantage over the current crop. So it is likely that new agents will either be active against resistant strains (like T20, or tipranavir) or an improvement compared to others on at least one important issue (like atazanavir and noting fewer lipid problems). That doesn't mean the new drugs will always be better in all ways - but at least in some they should be.

In the further look - there are new targets. Here the slate is more wide open - new targets and drugs mean plenty of uncertainty - at a minimum they provide activity against currently drug-resistant strains. Their safety profile will need to emerge over time but we at least have our eyes more open than before...

So, let me know if that did it, OK?



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