Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO;Fascinating! Stay tuned!!!

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

French Guidelines just killed Quatuor

By Charles-Edouard!

[Note: The Morlat report refers to the French Guidelines; Quatuor is a large, 640 patients, trial for 4/7 validation] The Morlat report (= French Guidelines) endorses ICCARRE (in 4/7, on top of that). Its update (May 2017) is here! You are informed (no one had told you ...). The text is chiseled. The term recommanded strategy has been avoided.

Strategy	French Guidelines (aka Morlat)
Darunavir 600/100 mg/j		as of today, [...] can not be recommanded.
bitherapy (IP/r + 1 INTI)		This strategy can be offered, [with] darunavir
bitherapy DTG/3TC		[pending] can not be recommanded at this time.
bitherapy RAL + MRV		cannot be recommanded.
bitherapy IP/r + raltegravir		cannot be recommanded.
bitherapy INI + INNTI		Dolutégravir + Rilpivirine can be considered.
Monotherapy IP/r		monotherapy DRV/r can be considered.
Monotherapy Dolutegravir		is not be recommanded     [NdCh-E: we will get back to this!]
ICCARRE (4/7)		Case by case[...] 4 or 5 days a week can be considered

France authorizes 4/7: period!

This as arm wrestling: prepare for blows under the belt!

To Describe ICCARRE, without citing it is dishonest. It is a shame and an insult to doctors, volunteers, Science. Trump would twitt: it's a disgrace: it's shamefull rudeness!

It is not an expert report, but the result of a balance of power ... Between BigPharma, their 'experts', and the Savages. The Legitimists are merely the middle man.

Legitimists serve us the soup: check them up on YouTube. I threw up. I have vomited ... On the pretence of presenting Quatuor, it is a hymn to the status-quo, the over-medication. Truchis, his eyes fixed on the sidereal vacuum of a distant Quartuor trial, every day more distant. Look at his eyes ... One feels the evasion (full of inaccuracies). As for his explanation for the 'failures' in ANRS-4D, it has been cleverly, but awkwardly, cut off, at a time when he could only point out that the number of intrinsic failures is ZERO, to which he has already testified, and to which he can not escape.

And what about his publication in a scientific journal: we are still in the waiting !!! And around the corner: the letter to the publisher, in case the truth is concealed, is ready: just a postage stamp away. Nothing is published and we wonder why ...

Whatever: we, patients, retain the basics: Morlat authorizes ICCARRE (4/7), period!

Quatuor a pretext trial

ANRS-4D is missing a comparator arm. No comparator arm, no 'recommendation', no non-inferiority ... compared to an arm that would follow the default strategy (7/7). The intellectual and moral inferiority is to ignore the comparator arm available: the huge cohort of patients under standard treatment. Or, equally, the patient's history. ANRS-4D has ZERO intrinsic failure, ie better than cohort results! And, even accounting for the 'pseudo-failures' (4%), an allowable margin of 12% (see the DOMONO calculation), and assuming that the controls are 100% successful, the non-inferiority threshold is at 88%. As there are also failures in the controls, the allowed threshold is well below 88%.

Any strategy with a success better than 100% less the margin of error (eg 12% therefore 88%) is non-inferior to the absolute: what else ???

The most stupid 'expert' will understand. The 'experts' are not stupid, far from it: they go to the manger. What forces Quatuor, it is the lack of connected neurons and of force in the arm wrestling ...

Quatuor: an unethical trial

Quartet is late, badly designed, hybrid (presence of Stribild® / Genvoya® !!!), and with a delayed arm, to the obvious harm of the poor volunteer!

Should only one of my readers participate and I would be in despair. I do not even imagine stealing the spot of a poor unfortunate for whom Quatuor is the only opportunity to benefit, at long last, from a strategy ... already authorized! And worse, for those who can not enroll! There are only 10 spots per participating French hospital!

What about informed consent! Are they going to tell candidates that they will, exceptionally, benefit from a new strategy, that is already authorized !!! When the candidates, already put on interminable waiting (it is already 1 year late), will be assigned to the delayed group, they will do as they please, either ICCARRE on-their-own or show them a well-deserved middle-finger.

And by doing ICCARRE on-your-own, or, at most, with a doctor (I added 2 to the list) of which no one can argue / prove that there is a risk, they will actively participate in building this a balance of power which is the only one that has proved effective in making Morlat (French Guidelines) surrender.

Your activist ICCARRISM and testimonials are welcome!

French Guidelines just killed Quartuor. Did they kill this blog?

I asked myself the question ... Since our subject is the weekly schedule, the authorization of 4/7 increases our potential readership, while it reduces that of the conventional ICCARRIENS. So the tailwinds are for us.

Good ... Gay Pride this Saturday and breaking the fast (end of Ramadan), this Sunday: Weekend of festivities and enjoyment: good Weekend, good fuck and not too many drugs!

Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO;Fascinating! Stay tuned!!!

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

Absolutegravir

Absolutegravir

Our readership explodes: we have new projects, we need help! we are looking for translators and also voices for podcasts. Someone to animate via social networks would also be of great help! You like this blog, so, please help!

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

Absolutégravir

By Charles-Edouard!

Not seen on TV, drug-induced Suicides and Insomnia ...

Déjà Vu ... Time and time again! First, beware of depression and the suicidal ideations induced by bad medication: it does not warn you and it is serious, even mortal. Of course you know where it comes from. Beware of Russian medical roulette: we try a combo, then another, then another: it is a trick of Septits doctors. Beware of drug overload: antidepressant, anxiolytic, sleeping pill, when you already take massive doses of 3 molecules... A priori, without this being a medical advice, you could begin to consider the Short Cycle (you are already eligible for the FOTO mode) ... Well ... Let's see what the future holds:

Absolutegravir: a new kid on the block

First, it's a ... -gravir. According to the naming rule that identifies molecules, it is a (preferential) integrase inhibitor. Here is one list. -gravir is one of the newest.

Same as for horses, there is a first-letter rule, in the order of appearance. We have: Elvitegravir (Gilead); Dolutegravir (ViiV); Cabotegravir (ViiV); Bictegravir (Gilead).

And to all honorable lords, I take, in order, the letter A, which I make follow with a consonant. So, gentlemen of Pharmaceutical Marketing, take note: the letter A is reserved for Charles-Edouard!

Why 'Absolut'? Certainly, I like vodka ... And as Absolutegravir is a dream by fellows of good company, a little crazy, so, it falls very well.

Absolutegravir: born in a flash of lucidity by Wainberg / Raffi

Wainberg / Mesplède and Raffi have published a prospective opinion: What if HIV were unable to develop resistance against a new therapeutic agent?.

Wainberg and Raffi are accustomed to the manger ... We may expect a panegyric in favor of DTG. However, this opinion dates back from 2013, and foresees everything that the clinic will subsequently observe (Achille's Heel (2015), success in naïve patients (2016), etc.).

No resistance? Yes! There is a heavy gun fire by BigPharma, whose evergreening policy (drug market deployment at a good timing) is based on the concept of multi-therapy. Monotherapy is the programmed end of the goose that lays the golden egg!...

Absolutegravir = zero resistance, zero, zero, zero

Obviously, any resemblance to existing or past molecules is purely coincidental. We put this at the end of scenarios inspired by actual facts, so as not to be bothered.

So, Absolutegravir, is not DTG. We're clear on that.

Unlike other ARVs, discovered by trial / error, it is computer-generated: Integrase has been digitized (see this 3D animation), and a docking software tests millions of configurations, sticking as efficiently as possible to the integrase, occupying a spot that the virus so badly needs. Sorry My Lord, this seat is not available...

A first pass is made with a non-mutated 'wild-type' Integrase and then re-done on mutated integrases until the ultimate molecule (s) is found.

A further screening is then carried out to ensure that the molecule does not (or little) stick to common enzymes, to be more specific, and to avoid side effects. This is made possible because many proteins / enzymes have also been digitized. It costs a lot, but we have plenty of cash, because our previous baby was the blockbuster of the last century.

As usual, we add a molecule (eg a fluorinated bridge) that the liver has a hard time to break, resulting in a very long plasma half-life ... It is useless except to generate billions of profit. Go ask Gilead, these are the Kings of the Fluor Trick and the Kings of Oil!

Absolutegravir: how many milligrams?

Because there are no side effect, and you will want to be successful in commercialization, you dose it to the max, but less than older molecules. Say, 50 or 75 mg should do it ... In Phase II, 2 or 10 mg it's quite enough, but we do not care about Phase II trials! In 20 years, we can release a cousin, 30 mg, and extend our profits for another 20 years!

Afterall, the dosage is, ultimately, the responsibility of doctors, not pharmacists.

There is no resistance: non-compliance, fortuitous or planned, has no consequence: too few, then VL goes up, and we crank up the dose a little. In short, we manage the way diabetics do: a drop of blood and we manage; In the end, we find the optimal and there you go: we have an optimized treatment, personalized, insensitive to non-observance.

Absolutegravir and the Darwinian black hole

Absolutegravir does not select any resistance. The Darwinian black hole, which appears when a main mutation leads the virus to a replicative dead-end, is irrelevant here. It is a concept of the era before, the world of yesterday, DTG and its R263K.

As it is personalized, by the doctor (useful maybe, but not indispensable), we come from all Europe to see these miraculous doctors, who make the big bucks!

Absolutegravir: when should we expect it?

Absolutegravir is the atomic bomb on the market: the day it comes out, we earn royalties for 20 years, but after these, it is over, finished. The epidemic is over, the drama is finished, and the goose that lays the golden eggs is dead.

Absolutegravir will be the last molecule to appear on the market, because it will kill the market, and we, as the owner of the perfect molecule, will only put it on the market when we have exhausted all the tricks to extend our huge profits.

Life is beautiful

Good Weekend, good fuck, and not too many drugs (licit or not ...)

Our readership explodes: we have new projects, we need help! we are looking for translators and also voices for podcasts. Someone to animate via social networks would also be of great help! You like this blog, so, please help!

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

Eclipse's Equation

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

The Eclipse and its beloved Equation

By Charles Edouard!

We publish, at the bottom of this post, 3 comments/contributions by Dr. Leibowitch. Read them!

Your testimonials are useful: here is one exemple ...
The START trial offered Freedom, to anyone who so wishes, to treat, without waiting. But to treat blindly, without discernment, is a collective hysteria. The allevaition is also made without any ratio condition (see Dr de Truchis). For Mono-Tivicay® see Dr Lafeuillade, in Toulon.

The Eclipse is not the one you think!

People have trouble understanding the Virus' Eclipse, that is a fact. Here is a rather classic view. (I have, in preparation, another version that will blow your mind ...)

According to a conjecture by Pr. Siliciano (2003), the reservoir is the cause for the rebound and this reservoir decreases only so slowly that there is hope to see the end of it. This is a vision of the twentieth century, already so ancient ...

In a recent publication (Hill et al., 2014), he has designed a model, in his Laboratory, that good common sense commands: rebound is a stochastic phenomenon (random in time), greater (long)as the reservoir is smaller. It is a classic Poisson phenomenon, nothing new under the sun... Slim Fourati made early interesting findings, as early as 2012. Bruner and the Silicianos show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. 75-95% of the reservoir is junk. (and so are the rambling rhetorics by Pr. Rouzioux-des-Critères ... Let's not be distracted ...). See also here.

We would like to be able to predict the Eclipse, have reasonable expectations and ditch the Great Priests of Immediate Resurgence.

We know two components: a pharmacokinetic wash-out + an exponential kinetic of reseeding. The deeper the suppression, the further below this kinetic will restart from.

In a short cycle, the ON period deepens the re-suppression. Does it allow you to go the ultimate bottom? We do not give a damn ... By the time you cogitate and you are already at the Week-end break (or 4/7, 2/7 ...).

CD4 susceptibility

The CD4 is more or less receptive, depending on the relative position of the CCR5 co-receptor (or even XR4 in the case of bi-tropism). Cells without CD4 receptors (eg, neurons) are unaffected. If the CCR5 is blocked by delta 32 (homozygous or heterozygous), the susceptibility decreases, or even becomes zero, as has been induced in the Berlin patient. It also decreases after activation has cooled down: therefore we wait a little before entering the Short Cycle.

The natural immune response (CD8)

Elite controllers are here as a proof. Found rarely, the HLA-B * 27 or HLA-B * 57 alleles increase the generation of keys, thus the arms race runs less to the virus' advantage. The immune response, say, to the level of an induced CD8 efficiency (I simplify), exists. Got it.

The size of the reservoir

It is a catch-all drawer, poorly quantified, but, obviously, the rebound comes from it, and, until further notice, we admit its existence. It is quantified so badly that any attempt to use it as a 'criterion' is a first-order stupidity (see comment # 2 by Leibowitch)

The quality, the viability of the reservoir

75 to 95% of the code that inserted itself in your genome (you're a GMO!) is junk, shit, you name it... (as shitty as the rambling rhetorics by...I do not have to repeat myself, we have understood). So it will not serve as a bootstrap. We know how to play on this percentage ... If you treat during the acute phase, the percentage of competent DNA is low ... It does not help us too much: we can not redo the patient history.
It evolves according to the molecules. Wainberg provides a convincing example. So, in order to prepare for a remission, albeit partial, some molecules are better than others. This is taboo ! We'll get back to it!

A basic equation

The time-to-Rebound is the inverse of susceptibility, of the reservoir (quantitative) and in proportion to the natural response and the proportion of Junk.

So we have :

Eclipse = wash-out +

(proportion of Junk x immune response) _________________________________ ( Proviral DNA x Susceptibility)

+ etc.

There you go! Not everyone is in the same boat, and it changes over time; The case-by-case recommendation, in the Morlat report (aka French Guidelines) is going to be very difficult to assess by the doctor. She does not have the tools nor the charts to interpret them ... (see comment # 3 by Leibowitch)

We will soon see how to turn this to our advantage and put remission back on the table.

Good Weekend, good fuck, and build your stock: France is heading to social collapse!

Comments (Dr. Jacques Leibowitch)

Comment # 1 by Jacques Leibowitch 12 June 2017

Comment # 2Jacques Leibowitch 12 June 2017

Comment # 3 Jacques Leibowitch 12 June 2017

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honor is saved

honor is saved

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Lanzafame saves the honor

By Charles Edouard!

In pursuit of the keys of Freedom:

It is important, especially at the beginning ... As for the 'case-by-case' basis, the question that comes just next is which is OK, which is not, not to amalgamate everything and find the Keys to Freedom ... And there, you need Science! And people who do Science!

Dr. Lanzafame made not too ambitious proposals, which were taken up on a very large scale. Well ... OK, I agree, ICCARRE should have saved the world: American invention, improved by Leibowitch and used ... nowhere outside France (for now ...). At the ANRS rhythm, overmedication and induced suicidality have good days ahead.

The Lanzafame report is of global scientific importance.

An analogy, a perspective

Let's try to be concise and clear: a strategy may be proposed to people who have already had (maintenance or secondary) and / or have people who have never taken anything; It can also be proposed to symptomatic and / or asymptomatic patients. Nice exercise of risk / benefit balance.

Merely an analogy
Cardiovascular	HIV Infection
Trial as Primary	Trial with Naive patients
Trial as Secondary	Maintenance trials

I take, as an analogy, the same exercise, from another context. The prescription of statins (to reduce cholesterol) can be offered to a patient, say asymptomatic, who did not take it before; And also in a victim of a cardiovascular accident. The first is called primary prevention, the second is secondary prevention. I hope you can see the parallel.

BigPharma promotes the (futile) primary! Cochrane and Prescrire say, basically, primary prevention is futile, and that, ultimately, perhaps, secondary prevention might be helpful ...

The excellent Dr de Lorgeril (the Mediterranean diet) makes us loose our virginity here on his blog (French Only): OK to make a distinction between a trial as 'primary' and a trial as 'secondary', much easier to realize, since you have the patients. And especially, a new infarction is frequent (often we get the same shit more than once). Fewer patients, more data. Easier job...

Nevertheless, Lorgeril explains, there is no need to distinguish between primary prevention and secondary prevention: it is futile in primary and it is just as futile in secondary ... Why? Because the underlying mechanism is identical.

That's what I'm getting at. There's no difference between the two, because the mechanism is the same. Let's get back to our subject ... If the underlying mechanism is the same, then we should have a consistent reading between the attack and the maintenance: it's not!

one-only mechanism		distinct mechanisms
Cardio (statin)		HIV InfectionMono-DTG
Primary Prevention	Secundary Prevention	Initiation (Naives)	Maintenance (selected)	Maintenance (unselected)

They try maintenance Mono-Tivicay ® in patients without problems (no failures, no nonobservance, etc ... not too risky), without selection (no rule like the Achilles' Heel). It's DOMONO, which does not work very well. It is BMM + P that does not work too well except for a selection algorithm (Achilles heel). The 'logic' in the head is: if one can not envisage it as 'standard' maintenance, how to consider it as First Line?

BigPharma exults: Adios mono-Tivicay® as maintenance and therefore as First Line!

It seems 'logical' ... No discussion ... End of file ... Yes ... Well ... That is 'If the mechanism is identical' ... If the mechanism is identical. That is a big 'if'...

The Lanzafame report (initiation) and DOMONO (maintenance) are small scale, so we are carefull. But, if ... it works in blind initiation and not in maintenance (blind), it means that the mechanism plays an unexpected role, to be clarified, to formalize and to use wisely, for a maintenance 'without failure'. Achilles' heel? Something else? We will see ...

One can not think of biology without Darwin ... On a territory, a mountain, unexplored, unchartered, if you arrive from the North or from the South, it is not the same!

And the benefit for patients also. Well .. I hope you see the picture! The debate, shunted for a while, is revived: is the Mono-Tivicay® enough for the naive patient?

This is crucial. Bah... The pretentious Parisian virology (a little greased, maybe) is of no use. The Kings of Garches are not on the spot. Wheareas, science is at stake!

You notice that Lanzafame has only taken the INDUCTION path, but not the MAINTENANCE path, unlike the others, that is his genius! And who has the fewest failures?

Lanzafame also saves the world ...

Lanzafame saves the honor of Medicine. It also saves the world (see next post) ... And we will address the ethical aspect: this will be sporty!

Good Weekend, good Fuck , No-Condom if <1000, and advocate for PreP, on the occasion

Comments

Samy 2017-06-12

Our readership explodes: we have new projects, we need help! we are looking for translators and also voices for podcasts. Someone to animate via social networks would also be of great help! You like this blog, so, please help!

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