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Re: Treatment Options

Feb 1, 2003

Dr Cal, You wrote "But a third option is to switch off of nucleosides entirely and just take a dual PI combination. There is info to suggest that a combo of just 2 PIs - the most studied so far had been ritonavir/saquinavir but there are other more "modern" combos to consider - may have less lipoatrophy than some other combos - including those based on nucleosides. So for example if the PIs are active drugs for you - an option might be just kaletra and saquinavir - a combo fairly well studied to be active, and at least may be of interest in minimizing further fat loss based on what we know now."

I have read and re-read this many times and it sounds like you are suggesting using just two PIs. I thought you were ALWAYS supposed to use at least three drugs and that Kaletra only counts as one drug.

Response from Dr. Cohen

You are correct - that's what the initial party line was - always three drugs. And we got to that conclusion based on first trying one nucleoside antiviral drug at a time (AZT, ddI, etc), and then two at a time (AZT/3TC, d4T/3TC, etc) and then when the third drug was added - whether it was a protease inhibitor or a nonnucleoside or even a third nucleoside like abacavir - we did see startling, impressive and durable control of HIV far beyond what we saw when combining the two drugs. So then where does my alternative come from???

About the time that the protease inhibitors were introduced - a study was done to see if two PIs just by themselves were sufficient to control HIV. One way to think about this is that it isn't just the number of drugs, but their potency. And so if a PI is about a potent as one and a half nucleosides, then perhaps two PIs would work. While it was an innovative and even bold move to study it - it did work. And it did prove that 2 PIs just alone can be enough to control HIV. The rule of 3 drugs was based on which meds we were using. For some drugs - two was enough. And this has actually been verified in several studies over the years. For example, one study years ago showed the combination of just Sustiva plus Crixivan to be just as powerful as AZT/3TC/Crixivan. Sometimes we don't need three drugs...

Now there are times when we might want three drugs despite this success with two - for example if someone has a high initial viral load and/or low CD4 count we might be even more careful and always use three, or even 4 meds to gain control. But outside of these situations - we have clear info that proves that some 2-drug combos work, and work well for years.

While the studies of these 2 drug combos are available, they have not caught on in any "official" guidelines as recommended. And that is mainly due to the size of these studies and what has been compared with what. And guidelines are created as relatively "conservative" documents and don't recommend things that have good info unless there is substantial information to support the approach. And as it turns out - we all have different definitions of what "substantial" means. One person's ample is another's inadequate... got it?

So yes - there is info to show how 2 can work. Indeed, there is even some very quiet research work going on about not just 2 meds, but even testing to see IF we can bring it down further... so stay tuned...

Early treatment didn't work
Epivir Once Daily

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