Resistance is not inevitable--What do you think about this interview??

[HALOO]

An Interview With Joel E. Gallant, M.D., M.P.H.

I don't see resistance occurring for no reason. Everybody I've seen who fails therapy is either failing because they're not taking their meds or they're failing because they have pre-existing resistance. Either it was resistance they were infected with or resistance that occurred while on a previous regimen. People who are starting therapy from scratch with a normal resistance test, those people aren't failing.

Bob Siliciano from Hopkins [Johns Hopkins University School of Medicine] presented some data at this conference showing that when you're on Atripla -- he used Atripla as an example, but I think it's true for any of the good regimens -- and your viral load is undetectable, it's truly undetectable. There's really no evidence that the virus is replicating at all. He showed that by adding additional drugs and not getting any further suppression. If you were able to measure your viral load using an assay that got down to one copy, you might see a viral load of, say, five or 10, but that's not really replicating viruses, just virus that's being released from reservoir cells. If there's no replication, then the virus isn't mutating and it's not developing resistance mutations, which means there's really no limit to how long one of these regimens could last. While you may not stay on the same regimen forever, because new drugs come out and things change, you wouldn't necessarily need to change because the regimen was failing.


http://www.thebody.com/content/toparts/art49232.html

[joemutt]

Why should it be inevitable? 

[John2038]

It is hard to identify the real  cause a VL of let say  5-10 cp/ml

This study have showed indeed a decrease of the number of infected resting CD4
http://www.journals.uchicago.edu/doi/full/10.1086/518254
so comforting maybe the idea of Siciliano when he says:
If you were able to measure your viral load using an assay that got down to one copy, you might see a viral load of, say, five or 10, but that's not really replicating viruses, just virus that's being released from reservoir cells.

Now those with undetectable resting CD4 interrupting haart always get a VL rebound.
So the virus is replicating somewhere else, otherwise, sooner or later, we will have eradicate the virus.

In this article:

http://www.sciam.com/article.cfm?id=can-hiv-be-cured

We can read:

Most AIDS research has focused on helper T cells because they circulate in the blood, which can easily be drawn for study. Recently, however, investigators have come to realize that other immune cells infected by HIV—macrophages and dendritic cells—may also contribute to resurgence of the virus after HIV therapy is halted or after the virus becomes resistant to it. Less is known about macrophages and den­dritic cells because they are located strictly in tissues, but recent findings suggest that drug therapy may not totally stop HIV reproduction in these cells. The level may be too low to result in the virus reaching the blood in detectable amounts. It may, however, be high enough to reach nearby T lymphocytes and to continually restock the reservoir of dormant infected memory T cells. Also, some infected macrophages seem to evade being killed by the virus inside them or by other components of the immune system. Macrophages, then, may sit ready to pump up replication when drug therapy stops.

How much these potentials replications can be the cause of the emergence of new mutations, the mutation of a r5 virus to a x4, the reversion of some mutations (eg 184), etc ?

So maybe should we wait much more to eradicate all infected cells ?

Not really. First because as long as there are on going replication, we can't empty the latent reservoirs.
In more, it seems that HIV can re-emerge from a single cell (http://www.medicinenet.com/script/main/art.asp?articlekey=93546):

In the new study, Gunthard and colleagues examined the AIDS virus from 20 patients who had gone off their medications for two weeks at a time as part of a study. By examining how the virus evolved over time, the researchers found that the disease can emerge from a small number of cells, or even a single one, when medication is stopped.


Generally speaking, the statement of Dr Gallant is like the Swiss statement: hard to verify

But the good point is that doing such assertion can cause a debate on it.

The reasons of failure can be multiples, and so it's hard to demonstrate anything
For eg, what if the use of drugs over a long period of time cause malabsorption, which could lead to drug failure ?

[Patrick]

John, if the virus is replicating at low levels somewhere in the body while blood levels remain undetectable, then that is because those cells are not exposed to the HAART drugs.  And if the virus infecting those cells is not exposed to the drugs (because HAART cannot reach them, thus no cure from HAART) then virus in those reservoir cells lacks the necessary impetus to mutate and evolve around the current HAART regimin.  Therefore, no resistance will occur.