Pre HAART therapy
Feb 17, 2002
Dear Dr Cohen, prior to HAART therapy, did anyone anticipate that the mono/dual therapy using AZT would only be able to prolong the lifespan for PWAs for 1-2years? Or were they anticipating that it could last much longer but then it turn out not to be? What are the major differences between the two therapies that lead some of us to 'believe' that the current HAART therapy will last longer (of course with proper adherence, no prior resistance and so on so for as well as the fact that HAART has been around for about 6 years). One last question, there are 2 schools of thoughts, one by Dr Silliano who believe that resistance will not occur once the viral load is suppressed to an undetectable level and another by Dr Ho who believe even with undetectable level there are still replication process which would lead to drugs resistance, in another word, resistance is inevitable. Exactly which one makes more sense to you? Thanks in advance!
Response from Dr. Cohen
The pre HAART era can be defined as the time when treatment was with one or dual nucleosides RT inhibitors (AZT, ddI, ddC, d4T, 3TC, and before abacavir was around). And while we didn't even have viral load measurements, we did note that treatment was temporary. This was clear based on measures of the Cd4 counts, which went up and then down again... or a measure of HIV itself called p24, a protein of the virus. Same thing - it went down and then up soon after. We knew treatment was not long lasting - we knew this since people still got sick despite our combinations of the time. The controversy of that era that peaked before the understanding of HAART was around whether these even temporary benefits of treatments were worth much at all in anyone except someone with a cd4 count below 200 -- above this count, the concern was that the benefits would fade away before someone "needed" this temporary help.
Well, as you know, HAART was the name given to a very different outcome. Two things happened. One, viral load measurements became available. And sensitive to low levels. So we could, for the first time, 'see' what we were trying to do - stop the enemy. And we could see if we were successful. Second, is the understanding of how resistance would thwart us unless we used at least two potent drugs simultaneously. Since it is not just the number of meds someone took - it was whether enough of them were potent and working. And that key insight, plus the availability of the newer meds: protease inhibitor class and the nonnucleosides, led to a series of combinations that showed us what happened when someone took at least two if not three active meds - HIV appeared to stop growing. For months. Then years. And with it a dramatic recovery of Cd4 cell counts, lasting even longer than HIV suppression itself in some cases.
But how long will this last? Since HIV ain't eliminated by this, just controlled. Will this last decades like we need it to -- since the average age of people with HIV infection is about 40? Well, you point out that under the surface of a viral load test result inaccurately labeled as "undetectable", HIV is detectable. And the question then is, since HIV can still grow, will resistance still emerge?
The short answer is that, if it will emerge, it sure is taking its time about it. Since there are enough people in long term studies of up to 5 years, in which HIV remains controlled. So, if it lasts 5 years despite HIV growing at these low levels, does that mean that we have a stalemate that can last for 50 years? And that is where the guesswork comes in - since we ain't there yet. But it is fair to say that HIV rarely does something slowly - and so our assumption is that if HIV could create resistance in that 5 year period it would do so. Since it hasn't, maybe it can't. And that is where this optimism comes from. Maybe it can't.
So we shall see. That is why it is helpful to have these virologists looking below the surface - to see what might be coming. But so far, so good....
The one thing that hasn't changed of course is the controversy about when to start. But now it is based on a different premise - which is that we can stop HIV even if the Cd4 counts are about 200. So how far above this count should we start? The confidence about treatment creates a very different feeling about this issue, even if we are still engaged in a similar discussion...
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