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



Provirus and histones

By Charles-Edouard!

Dr. Lafeuillade wrote: a doctor should never say that... and even has a website to present his book. One of us has read it...


Lafeuillade named Hypodolu the Mono-DTG in 1/7: it is a lightening. He proposed it (press release); he talks about it a bit here; then, he didn't talk about it anymore... Did he screw up? In this case, we would have liked to know... For me, it was a big mess (Mono-DTG 150 mg, 1/7), whereas Mono-DTG, in 7/7 at 50 mg, then 25 mg then 12.5 mg and also 50 mg in 4/7 had worked well... Some patients fail with Mono-DTG, without integrase mutation (cf DOMONO): can we have a major failure with Absolutegravir? This press release and its presentation at CROI-2018: DTG resistant mutation without genomic integrationcould enlighten us! Well... I'm not too worried... The patients have all successfully deleted... Well, thanks for this information, we'll come back to it! Until then, let's review our classics...

DNA, chromosomes and pads (histones)

Prof. Even knows how to popularize this whole thing: it will appear in his next book, so I'll make it short... DNA is this long double helix thread: it measures 2 meters, which for a cell is a lot: at our scale it would be 20 km. We can imagine it perfectly rolled up in the chromosomes, like a sausage. It is more complicated than that! A very good presentation can be found here. This video explains and also this one how a segment of DNA, integrated, can perfectly not express itself naturally. The buzzword isepigenetics...

P-H Gouyon explains it with simplicity: the DNA contains the recipe of the apple pie... But it is not the recipe that makes the pie: you need the ingredients, the baker, the opportunity to make it, etc.
Pr. PZ Myers puts the role of epigenetics and genetics into perspective...

The received idea that DNA is a protein factory has been challenged by Pr. C. Lewontin(the triple helix): the message is finally getting through... It is enough to remember that our heart cells have the same DNA as our fat cells. But they are different. However, there is always a tendency to think that expression will inevitably occur, and even quickly. This is not correct.

Proviral DNA is the king of napping

Once it has written itself into the genome of a CD4, the provirus is encapsulated in a histone (the pad), it is even protected by a chemistry called methylation. This methylation is a barrier, not the only one, to the expression of proviral DNA. When the CD4 is activated, excited, it will happen quickly. After several months of treatment, everything calms down and we go to the latent state.

Latency

We are told that the reservoir is in a latent state, but we are not told that of the fact and during the latency, it is, obviously, useless to treat. It's like putting weed killer on top of the snow: it's a total nonsense! To laugh, we can have fun with the hysteria of Pr. Rouzioux-des-critères...

Shock-and-Kill strategy

In a next post we will see how this methylation and winding in histones are the target of Shock-and-Kill, proposed by Siliciano, and implemented with histone deacetylase inhibitors, permitted but very dangerous.

Choke-and-Mute Strategy

The strategy behind ICCARRE is to drop a bomb and then leave its place to silence. It is natural, economical, ecological, epigenetic and proven. It leads to a dynamic remission for all. We will see, later, the mechanisms.

In the news

The headline is tantalizing: Australia on the verge of eradicating cervical cancer. To date, the incidence of cervical cancer has not changed one bit! If this hysteria leads to the disappearance of HPV, a cause of discomfort in Homo Sapiens Homo, why not? It is indeed a real benefit to others, for a personal benefit not demonstrated.

The French genius

- No man is a prophet in his own country: ICCARRE will be presented at the VI International Eastern Europe and Central Asia AIDS Conference 2018In Moscow, where the need is great: Possibilities of interrupting therapy in patients with sustained HIV suppression.

- In 1913, Apollinaire read... Apollinaire: Under the Mirabeau Bridge... (France Culture).

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good weekend, good stuffing and not too many meds ... Huh?

Long Vacation

A long vacation

For a long time, this blog has not been translated into English. We are resuming translation and you may go here to read the next translation, or jump here for the latest translated post

099

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



Healing: 3 proposals, one of which walks

By Charles-Edouard!

Joëlle's testimony

You are making progress, my dear, you are making progress! Think about the frequent resumes, and give your news.

Healing: 3 proposals

Around 2003, Robert Siliciano theorized that a cure would be impossible. Until recently, there was only one proposal for remission, that of Siliciano, based on his theory of the reservoir: unchanging in its content, stable in its quantity.

In fact, there are 3 theories of reduction of the operational reservoir, therefore, of the functional cure.

A- Siliciano theory

The reservoir is constituted as soon as the primary infection occurs, and does not change (or only slightly) in its content: it always contains the active virus (most often wild). The only way out is to decrease quantitatively the reservoir to hope to play Visconti, for a few lucky chronic patients. One thing leading to another, he developed a proposal for a quantitative reduction of the reservoir and obtained funding for laboratory trials. The strategy is sold to the funders and made popular under the name shock-and-kill.

B- the Wainberg theory

With Dolutegravir one can modify the content of the reservoir(read here) to introduce R263K, which reduces the reservoir until it disappears: Wainberg has done lab tests (read here) and proposed a cycle of progressive attenuation of the reservoir(read here): his proposed cycle is not consistent with his theory, however, it is possible to think of an alternative cycle. This is how yours truly had succeeded in some things but not in the proposed cycle: the proposed implementation is not very practical, but the substance is good: we must advance this way, which is the first laboratory proposal to challenge Siliciano on his ground, and offer us a perspective...

C- the Leibowitch / Sonigo / Charles-Edouard theory

Sonigo is a golden-boy of French biology... He explains the Eclipse to Leibowitch as expected and necessary: he tells us that this is what happens(see the graph), without the theory being explicit(if you read Kupieck and Sonigo, you understand the spirit). For lack of having been able to read under his pen a theory of the Eclipse, I was reduced to writing the Equation. I will therefore, in abstantia, write a stochastic theory of the Eclipse. It concerns the random events of resurgence: the afficionados of the series Death Note will be seduced(I will call it that). To put it simply, proviral candidates have a delay in emergence which is an intrinsic property of theirs: a kind of (over)life expectancy, well hidden as they are. With the progressiveness of the ICCARIAN descent, those who have a short hidden survival will be de-zoned at 4/7, then at 3/7, ... The reservoir sees the quickest proviruses disappear, only the slowest, the deepest, the most irremediable ones remain: the window always opens more and more, to close again, fatally, but then, after 15, 20, 30 days...

Burial of the DNA in the pads (histones)

Each of the theories is based on the burial of the DNA in the pads (histones): Siliciano wants to use histone strippers (e.g. Depakine!!!), Wainberg wants to move to deep histones, Leibowitch allows expression-prone histones to be dezoned: only proviruses buried in deep histones remain. Putting the 3 proposals in parallel allows us to identify a common theoretical core: burial in histones.
Prof. Philippe Even explains it remarkably well and we are impatiently waiting for his next book: it's inside! Failing that, I will do it for you: it is fascinating!

Parallels and implementation

It allows us to highlight the Leibowitchian proposal as being, to this day, the only proposal immediately availablecertainly imperfect...

A- Siliciano: attractive, but using dangerous openers (opening histones is opening the can of worms: cf dekapine): for the moment it is a failure! The patients treated in primo will be the best candidates. As it uses molecules, on an experimental basis, with the promise of profits, it receives subsidies from Washington.

B- Wainberg: attractive, modern (DTG...), demonstrated on tissues (in the lab), but difficult to implement: no known implementation (and I failed, need I remind you?). Mono-DTG patients will be the best candidates... As she makes DTG a healing molecule, she was receiving subsidies from ViiV, but well... Who to finance the end of her pension?

C- Leibowitch: counter-intuitive, unless one theorizes well, imperfect (because limited to 1/ Xmax). Advantage: its implementation is proven, costs nothing and the immediate benefit to the patient (even if it is capped). Patients who have passed the 4/7 are good candidates. If the ANRS was not so poor, it could have enriched the expertise of the Eclipse and made a major breakthrough... Well... no... We will have to do without them.

ICCARRE and dynamic remission

If the Grand-ICCARRE (1/7, 1/15...) is presented in this way as one of the 3 proposals in the running for remission, it still has more gumption than the anecdotal little drumbeat. Leibowitch doesn't care about the underlying cause of post-treatment delay and theories: it works and it suits him! I still don't understand how the proselytizers of the progressive, Darwinian method don't conceptualize that the Grand-ICCARRE is more than just an alleviation: it is a dynamic remissionthey have their finger on the most brilliant invention of the century, and, seem to look the other way

Well... We'll see next time what is the burial in the pads (histones)

In the news

- The Frenchjustice system nails the hepatitis B vaccine

The French genius

P-H Guyon explains, in a few words, at minute 1:11:40, the myth of Daedalus, the father of ICCARRE, who always has a technical solution to everything. He invented the extended prescriptions, the always more. ICCARE has a father: over-medication! Daedalus is a bit like Siliciano...

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97% of patients overmedicated, 22 million without treatment... Let's stop this scandal!