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About the virus
Feb 25, 2001

I would like to know if the virus transmitted now a days differs from the virus 15/20 years ago. In one hand you would think is worse because of resistences, and in the other it appears that is also less virulent because of treatments, or maybe I am totally confused about this matter, but I do wonder if recently infected individuals have the same response to treatments than people with strains of virus more naive to treatments. Thank you. Hiv+.

Response from Dr. Cohen

A very important observation to have made given what is written these days.

Here are the issues. After HIV started, it showed differences in its genetic structure. These have names like "clade" which differ in where they are around the world, and "polymorphisms", which simply means that, within a clade, there are multiple variations at a given place in the genetic structure. However - these changes do not alter the impact of our antivirals. These changes all existed before our meds arrived. After the meds got here - we started to see new genetic changes - these changes are the ones we measure when we go a genotype test. These changes do alter the impact of an antiviral medication - they make the medication less successful. This is resistance.

However, there may be a price HIV pays to create this genetic change. Some mutations do not "cost" anything and are just as able to grow as the wild type strain. However, there are some mutations that do "cost" - HIV cannot grow as well as the wild type. This can be referred to as a partial loss of fitness. It simply means that a strain of HIV that has these mutations does not grow as well as the wild type HIV. Therefore, some people who are on medications, and have resistance to these medications, will have a viral load that still is lower than what was seen before starting meds. There still is some effect of the meds - and this strain cannot grow as well as the wild type. And this partial suppression results in a lower viral load. Which also allows the CD4 counts to be more stable than they would be off medication entirely.

So does that mean that it is a good thing to have resistance? If someone is recently infected by HIV and has a resistant strain, is this good news? Sadly, the answer is no for a few reasons. First, while a resistant strain is less fit, it still can grow. And when it grows, it still slowly destroys our immune cells. It may take a little longer than wild type, but not enough that we can count on this as a strategy. Unfortunately, HIV can also "revert" back to wild type - and therefore someone who starts with a resistant strain can then in time also have a wild strain - and then have the worst of both worlds - the wild type does its usual destruction, and the resistant strains make treatment much less successful.

Here is the key - while a resistant strain may be less fit, it is still able to grow - that is why we can measure it at all - because it can grow. And when it grows, it destroys. And sadly, our meds are less able to stop it - it is resistant. So it becomes more like the situation before we had any effective treatments - we just watch the loss of cells and cannot reverse this like we can when we have effective meds. Since the most improvement to our immune system is seen when we fully suppress HIV - those are the people who do the best.

Now, you will read about maintaining meds as a strategy, even despite resistance. We do this to take advantage of the partial loss of fitness of a resistant strain, and the lower viral load we'll see. But this is still not as successful as a fully suppressive combo - we have not intentionally been able to create a strain that is resistant, growing at levels that do not hurt our cells, and then stop it from mutating further. Since HIV is in this to win - and it continues to mutate - sometimes regaining the fitness that some strains have lost.

Hope this clarifies this very important issue. CC



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