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Sunday, January 21, 2018

En route towards remission

This was originally published here, in French. We provide this translation for your convenience, practical aspects may differ where you live.

En route towards remission

By Charles-Edouard!

Well said!

Remission: the question resurfaces

I put the remission on the table, even if it may seem surprising. I am talking about remission following ARV treatment: it is the post-treatment control, usually considered impossible.

The debate took place in a context that has evolved a lot and the premises underlying the verdict are flickering one after the other. Today we can build an argument in favor of total or partial remission. A blogger's delusion? Not at all. For part the argument was exposed by recognized authors such as Wainberg, Ananvoranich, and even Siliciano. We will get back to this. Reader, take patience, read, and judge for yourself.

The dominant theory is Siliciano's. Very early, I made a note: "Siliciano is wrong". More and more facts invalidate the premises or conclusions by Siliciano. If it is false, we can consider that patients achieve remission, with and thanks to treatment.

Remission impossible: theory and history

Very early, it was found that when the treatment is stopped, the virus rises and we are not cured. This is our very first post: ICCARRE: Sir, you are cured! What prescience!

Robert Siliciano gives us a theoretical approach in 2003. He makes some hypotheses, over simplistic, on the dynamics of the 'reservoir', reduces everything to a single time constant, that he measures on some patients. He calculates an ... average ... of 44 months half-life, which puts the remission to 66 years of treatment: in other words, impossible.

Nothing has come formally to invalidate his theory. Nothing, really nothing ... Or so little ... A "so-little", which begins to expand. Inaudible yesterday, perceptible today, deafening tomorrow.

First, the discovery of "Viscontis": a handful of patients, early-treated, who keep the virus under control despite stopping treatment. Several attempts have tried to reproduce it (here and SPARTAC trial), without success. Why can't we reproduce the Viscontis?

Then came the idea of ​​reducing the reservoir by a "Shock and Kill", where a pharmaceutical treatment would wake up the reservoir, which the ARV treatment would then kill. For now, it has failed. Here too, the premises are debatable.

Remission and near-remission

The remission means to keep several years, without rebound nor treatment.

Fictitious example of a malignant cancer with "heavy" chemotherapy in 10 sessions: we survive and the cancer has regressed. The doctor suggests about 5 years remission, at most. Relief and disappointment too. The doctor adds: and if you accept an annual maintenance chemo, then your life expectancy is normalized ... Of course, this is not a magic remission in the strict sense, but still ... So we do ... Later, you can even do it once every 2 years.

He who can do more can do less: Can you imagine total remission even though you have not achieved 1/7? No, obviously! And if you have passed 1/7, can you consider the 1/15, as I showed here? Then 1/21, 1/30 and finally the 'true' remission. Me, I managed 1/21, but not 1/30, so I do not try the final step. Moreover, from 1/15, the remission has only little attraction. Frankly! At 1/21, you live very very well! For me, 1/7 remained a bit heavy. Others are happy with it and we understand them!

Remission finally possible: theory and evidence

- The example of HCV shows that we must not despair ...
- There are more post-treatment controllers than they would like us to believe, and who are unaware, as a hospital in Antwerp has demonstrated. Noone will tell you...
- We treat earlier, which may be favorable
- We have not been able to repeat Viscontis: theymay have done something that we did not understand, and that this something is important.
- Siliciano himself, along with Hill, questioned his own theory. He considers that the reduction of the reservoir necessary for a prolonged remission is less than initially thougth
- Wainberg theorized remission by the way of R263K and made laboratories trials: conclusive! (we'll come back to it: that's what I'm trying to do right now)
- The oral prolonged-release medication gives 7 days of medication (for a single dose) that is extended by a 2-week Eclipse (or even 3 ...) and that makes you a once-monthly!
- Leibowitch and his 1/7 have 800 years of proven pharmaceutical remission. With the hundred, or so, patients involved, there will be a few who will want to explore beyond.
- Biologists can not do Shock-and-Kill, while ICCARREs, in advanced mode, do it every day every week. Ah ... Yes ... Think by yourself.
- Dolutegravir should allow to do more (Too bad it is incompatible with NVP or EFV ... too bad ...): for some patients / viruses, it is an Absolutegravir. So...

On the road to remission

Unless you stay, stunned with fear, in a very uncomfortable standard treatment that is too heavy, too daily and above all too unnecessary, once you start 6/7, you've put a finger into it. Here is what can stop you:

- you don't dare explore any further
- the 1/7 suits you, you stop there
- the virus resurfaces

It is only a matter of time that a small group of people attempt the adventure, with only one obstacle: a virus rebound. It is also necessary to develop the technique that will weaken the reservoir and / or the virus. The Quadri by Leibo is a candidate. It's not enough, we need other 'bombs'. We are working on it. We have a lifetime ahead of us!

In the news

Towards DTG+RPV : Juluca ®: Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies.

Have a good Week, good fuck and do not abuse of meds/drugs

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Have a good Week, good fuck and do not abuse of meds/drugs

This was originally published here, in French. We provide this translation for your convenience, practical aspects may differ where you live.

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