I recently attended a debate between my physician and another physician, the topic was "hit hard" vs. "drug sparing", my physician argued for drug sparing. The consensus of the experts was drug sparing is the way to go. If this is the consensus of three of four physicians, why haven't the treatment guidelines been revised by DHHS and the CDC? What is your feeling?

Well, first some definitions. Since these days, it is possible to achieve both goals. But this is a big deal - so a longer answer...

"Hitting hard" refers to the result of whatever combination of meds you choose to use - it is not the opposite of drug sparing. It is the opposite of "hitting soft" - and here, "hard" and "soft" both refer the lowest viral load after starting whatever meds. When we aim to get the HIV viral load to below detection - meaning that it is barely growing if at all, that is the result of hitting "hard". And the reason this strategy is the dominant theme for a few years is that it is the best way we know of to get the longest benefit from whatever meds are used. Since, when HIV grows in the presence of our meds, it can "learn" to create resistant strains that ignore the meds. And these resistant strains can grow - and again cause damage to the immune system. And in the past years - when HIV can grow just a little - it tends to grow more over time. And do more damage. Thus the inspiration to not let it grow and damage at all - by hitting with a combination that prevents resistance - for as long as possible. That allows us to get the longest possible benefit from the limited repetoire we have. Since hitting hard is generally a means to an end. Which is to get a durable response. If we had a hundred or so different meds, each of which could work for a year, then we could use them one a time and maintain a normal lifespan. But we don't. We probably have two to three effective combinations from the current menu. And these combinations have at least the potential to work for years, and maybe decades. Which is what people with HIV need from the meds - decades of control. And so the need, given the lack of multiple options, is to get the longest possible benefit from whenever these meds are used.

While there may be a few reasons why a few clinicians still discuss combinations that hit "soft" and thus allow HIV to grow on the meds - this is done as a compromise rather than a goal - meaning that for some reason it is seen as too complicated, or risks too many side effects, to hit harder. (Note also that for those with very low viral loads to begin with, it may be possible that some combinations of just two nucleosides could be considered hitting "hard enough" since we have seen studies where those with low viral loads to begin with have some chance of getting below 50 copies. But we don't know how long that would last...)

Now - drug sparing. Usually this refers more to "class sparing" - meaning how many meds, or classes of meds (protease inhibitors (PI), nonnucleosides, and nucleosides are each a class of antivirals) should we use to achieve our goal. Initially we learned how to hit hard by using 2 nucleosides and a PI. This was the "nonnuke" sparing approach. Then we learned how to hit hard without using a PI - by using a nonnuke instead. That was called the PI sparing approach. And recently we have seen one combination of triple nucleosides that hits hard - and spares both nonnukes and PIs. Sparing two classes isn't entirely new - there were two studies of using dual PI's showing you could hit hard without either nukes or nonnukes - at least in the majority of patients with a viral load below 100,000.

So you can hit hard and spare meds, or classes of meds. And the opposite of drug sparing would be triple class regimens - combinations of nukes, nonnukes, and PI's. These would be the least drug/class sparing. And the reason to hit with all three classes is theoretically that if you did, the chance of success of the combination would be higher - so you would never need another combination in the future.

But this has been less popular than the class sparing approach - in which we save at least one class for plan "B" - if plan A doesn't work forever. For whatever reason. Why spare a class? The main reason is, again, resistance. If resistance should happen while on combo A - then not only do you need to worry about resistance to the meds used, but you need to worry about cross resistance. And cross resistance happens within a class of meds. So that if you spared a class in plan A - you can count on it working fully in plan B.

So it seems to me that the question isn't hitting hard versus drug sparing - but rather, since it makes the most sense to me to hit hard - what's the best way to do it in a well tolerated regimen that works for the long term, while saving something for plan "b" just in case...? And that's the debate of our time. No right answer. But options for whichever way you choose to go here...

hope that clarifies. CC