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Confused re: eradication of latent resevoirs?
Dec 31, 2009

Hello,

I was reading up on the potential for future HIV eradication thorugh the getting rid of latent resevoirs but was confused over several points.

1) As I understand it, HIV remains dormant in memory cells thus avoiding HAART. So scientists are learning how to flush out the virus so it can be exposed to medication. But I thought HAART only attacks viral reproduction and not the particles themselves. So would it not be better for them to lie dormant?

2) Is someone's undetectable load seperate from their resevoir/ Does it account for particles in the blood stream rather than living inside a cell? If it is still in their blood stream then is this because onc the virus is stopped replacating the remaining particles remain as HAART can't directly destroy them? If so, how can they continue living, do they have that long a half life?

3) I think I read that the resevoirs can be responsible for jumps in viral load if treatment is stopped. Is this true or is it just the less than 50 copies remaining in the blood stream?

What are your predictions for this field.

I'm 22 and have probably been infected for a year. Do you think I'll see a cure in my lifetime if I have no resistance and stick to meds?

And one other question.

I've read conflicting reports on adherence. I've read that so long as you stick to your dose there is no reason to see why adherence shall occur. But I've also read that its unusual to remain on one regimen for say, up to a decade, without changing. Is this because resistance usually occurs over a long period of time even with adherence, or just because people have switched to better medication in the past 15 years as it has become available?

Thanks so much for your insight

p.s. I'm not holding out on a cure, I'm determined to live for the day but it's obviously interesting to keep up to date.

Response from Dr. McGowan

Thanks for your great questions.

During its life cycle HIV inserts its gene (converted into DNA) into the chromosome of our CD4 cells. At that point it can do 1 of 2 things...it can make copies (which will eventually burst and kill that cell) or it can lie dormant. If it is dormant then it is just a piece of genetic code sitting in the chromosome, there may be no actual virus particle at all. This is what happens when the viral load is "undetectable". The virus is shut down from making new copies of itself. If you stop taking your meds, the viral genes in the reservoir can start to make copies and feed the whole infection again. That is why meds have to be continued indefinitely. If you restart yor meds, it may not save that infected cell, but it will protect the neighboring cells from being infected. The loose viral particles are quickly die off and are cleared away, they do not stay in the circulation. So the key to getting rid of HIV is to try to get that remaining bit of genetic code out of the resting infected cells. As you mentioned this is an area of active research. Having suppressed virsu would be the first step.

As far as adherence is concerned, the main thing is that you have to keep a level of medicine in teh blood over the course of the day that is adequate to keep the virus shut down. If the level drops due to a missed dose, the viral genes can start to make new virus particles from inside the infected cells in the reservoir and infect new cells nearby..without any medicine around to protect them. That way the infection spreads to new CD4 cells.

Best,

Joe



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