Dolutegravir and R263K

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

Our Summer 2017 series: DOMONO will have been, in fact, a real SUCCESS! - Dolutegravir and the R263K - the R263K: new scenario (DOMONO) - the N155H: new scenario (DOMONO) - Nevirapine and Mono-DTG Switch: the Hunchback Trap - calculation error in the primary hypothesis - DOMONO and the benefit for the patients (not for BigPharma ...)

Absolutegravir, Dolutegravir and the R263K

By Charles Edouard!

Some news from Backy:
A small pick up in ASAT is not a cause for concern; At 5 or 10 times the limit, yes, this would be worrying; You are far from that! This is a successful case of Tivicay® monotherapy; Once settled, you can watch what others do, such as jesuisdu13 who uses mono-Tivicay ® at 4/7 ...

When Dolutegravir mimics Absolutegravir ...

Here, I simplify greatly ... also reread our post on : Absolutegravir, a fantasized molecule.

Absolutegravir is computer-designed on a digitized 'Wild-type' Integrase; a docking software tests millions of configurations. Then, they rerun on mutated, digitized integrases; Finally, on common enzymes to avoid side effects.

In the computer-aided design of DTG, we do not yet have the digitized mutated integrases (besides, which mutations?). So DTG is designed on 'wild-type' integrase and confronted with known mutations of RAL and EVG. Its efficacy, which is assumed to be absolute, is specific to the unmutated 'wild-type' integrase. It is a good start, and more effective than the usual cuisine that gave birth to Raltegravir. Everything is a matter of timing ... I simplify to the extreme, in fact, it's a huge job!

The R263K: a deep Darwinian well

In the very first trials, we observe (by luck or design insight), a phenomenon quite unique in its extent, not seen in test tubes. The mutation of choice of DTG is R263K. It is hard to find in tests tube (known as 'passages'), but it is found in the VIKING trial and in tissue passage tests (a McGill, Montreal, exclusive)

This mutation has two characteristics: it confers a very modest resistance, almost nothing, and the mutated virus has only one desire: stay home: it has no ease to replicate: its low fitness makes it unfit. It's almost a 'Junk'. It falls in its hole and stays there, happily: Let's call this a Darwinian black hole or Darwinian well.

When the pharmacological pressure acts on a wild-type virus, it decreases (without mutating) or mutates with the R263K, which, remarkably, makes the pharmacological pressure even more effective. Conversely, when the pharmacological pressure decreases, the virus regains vigor, including, in the first instance, its R263K mutant. Further, by the effect of "survival of the fittest', the historical virus, wild-type, takes over and we lose track of the mutant.

On a wild-type virus, DTG acts as an Absolutegravir

As long as one remains within this binary system, R263K mutation is beneficial. It is a marker, an epiphenomenon, and it is not the cause of a VL increase (whereas the drop in pharmaceutical pressure is); It accompanies it, kicking and screaming, to finally disappear.

As long as you have a wild-type virus, especially on integrase, Dolutegravir acts as an Absolutegravir. The owners of Absolutegravir will want to keep their trump card until the end, and ViiV HealthCare is not going to come and explain that the naïve patient, with a wild-type virus, has a molecule that has all the advantages of an Absolutegravir.

This is how Lanzafame succeeds with his DTG monotherapies on naïve, selected patients, how I managed Hypodolu (overdosed), Minidolu (Tivicay® 1/4 of a pill, daily) and DTG + 3TC in 1/7

Here is a first clue for reading DOMONO, our summer serial!

Good holiday, good fuck, beware of the sun, and long live the Eclipse!

Comments

Anonymous July 17 2017


Charles-Edouard! July 17 2017


Anonymous July 17 2017


Charles-Edouard! July 17 2017




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

Our Summer 2017 series: DOMONO will have been, in fact, a real SUCCESS! - Dolutegravir and the R263K - the R263K: new scenario (DOMONO) - the N155H: new scenario (DOMONO) - Nevirapine and Mono-DTG Switch: the Hunchback Trap - calculation error in the primary hypothesis - DOMONO and the benefit for the patients (not for BigPharma ...)

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

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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.

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 ...)

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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.

Eclipse's Equation

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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

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Practical Guide 2017

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Here is an exchange, a rather bad one ... One says:
This is called 'close the door behind you', much like former immigrants opposing ... immigration. And there is worse: each and every one has his own restrictions, taboos: according to them, descalation is not for you if CD4 are less than ... If your CD4/CD8 ratio is less than ... If your reservoir is... If your combo is not X or Y ... Etc. All this is rigorously FALSE!

Without an informed, well-argued deciphering, it sparks in all directions: this is all FAKE-NEWS

A Practical Guide to Avoid Misunderstanding

Update of the Practical Guide SAFE 4/7: ANRS-4D introduces a PREMIUM eligibility and the Morlat 2016-2017 report explicitly authorizes ICCARRE, without any practical information, without citing all the trials, which would have been useful and honest. There is a great advantage: by saying nothing, it saves us the usual bullshit! Pr Rouzioux-of-criteria ate her hat!

The Morlat report is the usual useful idiot, silly and useless, unusable and unpractical. The reader, patient or doctor, is referred to just 2 trials, without the least bibliographic reference to ICCARRE. Morons!

This suits me a little, the patient searches on the internet and invariably gets to the Practical Guide, a very downloaded document, and for medical advise, on our list of doctors. She's out of trouble! Good!

The Practical Guide is enriched accordingly. It is available in French, English, Portuguese, Spanish (soon) and Arabic (indeed. It is not claimed to be perfect, nor to be a substitute to a doctor, expert-in-that-very-matter (Beware of incapable, ignorant, incompetent or liars and ... counterfeits)

The 2016 version differs from the 2015 version:

ANRS-4D revolutionizes the short cycle; The 2016 version therefore differs from the 2015 version:
- Eviplera® (Complera®) is tested: 100% successful
- Premium eligibility: Short Cycle is more appealing
- Direct to 4/7, under eligibility conditions: validated
- In patients, strictly eligible and strictly observant, the VL has never picked up: in this context, our rule of frequent VL can reasonably be reconsidered (even if I keep liking it, but I am incapable to prove it is indispensible

Looking at at the rare (very very rare ...) personal testimonies of failures, one inevitably finds failure to follow of one of the three rules: Efficiency, progressivity, frequent VL. And Shit happens ... Well, always easy repaired (eg back to 7/7) ...

Premium Eligibility

Progressivity: Well ... I prefer progressivity, because I went through the anguish of 6/7 (I was scared!). Perhaps useless, it did not cost me.

Frequent VLs: People have trouble with this; VLs detect a loss of efficiency as soon as possible. It is the other side of the efficiency coin. If one is sure of the efficacy, very sure, what about the need for frequent VLs (month-1, m-2, m-4, m-6 ...)? Okay... But true efficiency is proved with ... VL!

Efficiency: many presume drug's efficiency ... Yes, they have been given the latest very modern, very pricey, so well marketed that they neglected all warnings. This medicine, imperfect, is better sent to the sewer. ANRS-4D formalizes the Premium eligibility, which is already in ICCARRE (if you can decypher), not in the others, an additional proof that ICCARRE is not a simple sequel.

conditions	Simple Eligibility	Premium Eligibility
a priori efficiency validation	No	Yes (genotype required)
validation of usage efficacy	2 successives UD VL	3 times VL < 50 (make sure it is undetectable)
minimal duration of current ART	12 months	4 months
Advantages	no Genotype	4/7 direct frequent VL unnecessary?
disadvantages	6/7, 5/7; frequent VL	Genotype required or redone

ICCARRE method of to redo a genotype or regain sensitivity is stunning! It is a Septist's nightmare and,therefore a good reason to explore it! And we'll get back to it!

What about ANRS-170-Quatuor?

Announced for the end of 2016, then by act-up for July 2017, it will be good enough if it ever starts one day! We are being put off. Results for 2020! At best ... Well ... I hope noone is fooled by this little game.

It is merely the continuation of the ANRS-4D trial, which coordination had been entrusted to Mmes BENALYCHERIF and AMAT (phone: +33 (0)1 40 25 63 65, email: aida.benalycherif... followed the at sign then by ...gmail.com et karine.amat... followed the at sign then by ...hotmail.fr). You should be able to find more there.

Morlat already authorizes ICCARRE, then, what is the point with ANRS-170-Quatuor? What's the point?

This blog is not a medical advice: For this strategy, see Dr. de Truchis (see list). What about others? Well ... Why the copy when we have the original? Ignore the ignorant, and go to one of these docs, Practical Guide in hand. Move your ass! And report!

Today, is the first of Ramadan: our elders have understood the benefit of 'breaks', also of the Shabbat breaks. Since Copernicus, we have a much better understanding of rhythms! Good Ramadan to those who celebrate it, and Good Shabbat and Good fuck to all the others!

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.

First-line Tivicay Monotherapy

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

First-line with Mono-DTG

By Charles Edouard!

Here is a topical question:

For medical advice, see Pr Katlama or Dr. Lanzafame. What do the tests say? In monotherapy, in ING 111521, 90% of patients passed the <400 mark in just 10 days! Lanzafame initiates the Tivicay ® monotherapy, from the first prescription. As first-line, DTG + 3TC Bitherapy worked well. The proposals DTG + 3TC or Tivicay ® + Truvada ® are not coformulated: they allow monotherapy: just leave the other one in the closet. Dr. Lafeuillade recounts a personal experiment ...

Will the Wainberg hypothesis be validated by Lanzafame?

On a 'wild' (non-mutated) virus, the first mutation to appear is R263K. But it prevents the virus from regaining strength (loss of fitness), and, the reservoir should 'normally' decrease: it falls into a Darwinian black hole .... Adios asshole!

Conversely, if the virus has step-stone mutations or substitutions (I simplify), it can acquire resistance mutations; The benefit of R263K is lost, and that of mono-Tivicay® as well ...

If the Wainberg concept is correct, then, we should see at the clinic:
- a rate of success not too bad, not too good, on already mutated viruses (eg failure to RAL or EVG), and this is what we observe (Viking trial)
- a success rate, in maintenance monotherapy, which depends on the presence of the footsteps: this is what is observed in the BMM + P cohort: it is the Achille's heel.
- an excellent success rate, in first-line on wild type virus: this is what we observe (ING test 111521 + Lanzafame report)

If the Wainberg / Mesplede theory (the R263K pathway is beneficial) is accurate, the success of DTG monotherapy should not depend on any parameter other than wild-type (or not) nature.

Tivicay® Monotherapy with Naïve Patients: Yessss!

Hence the importance of the latest publication by Dr. M. Lanzafame, who further increased his group of patients using Tivicay® monotherapy as their first therapy (wild virus and a VL <100.000).

Lanzafame saves the medical honor ... and the world!

He has redone ING 111521: it is a prudent scientific approach, to confirm the results of a commercial trial... This is in line with the result of ING 111521, unexpected at first, then put under the rug or even occulted later.

He chooses his patients, with restrictive conditions on the virus, the 'wildest' possible. And none on CD4: one patient had CD4 = 1, another CD4 = 2!

Lanzafame unveils a new strategy. His patients (why not you?) will therefore benefit from an effective monotherapy, as first line, which opens the door to an alleviation like ICCARRE 4/7. His group will be able to move closer to remission ('cure').

He invites us to reconsider the results of BMM + P (Barcelona, ​​Montreal, Munich) + Paris, where, with selected patients, we have excellent results, contrary to the DOMONO protocol, where patients are not or poorly chosen, and where the result is mediocre.

Obviously, no one told you about this !! If the ignorants and traitors tell you that mono-Tivicay® does not exist, well, now you know that it does... The subject is relaunched from the ethical, clinical, public health angle: we will discuss this soon ...

This blog is not a medical advice: For this strategy, get in touch with Dr Katlama, Lafeuillade or Lanzafame (see list). What about others? Well... They are lagging behind, so you ignore the ignorant, and you go to one of these 3 doctors. Move your ass! And report here!

In this election weekend many will have to swallow a bitter snake...
Not me! This weekend is my first without meds: it is the first of my return to 1/14! And it is real cool!

Comments

Nanar May 21, 2017


Charles-Edouard! May 21, 2017



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

beyond 1/7

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

The other side of the 1/7 mirror

By Charles Edouard!

A tribute to Patrick Valas, the first ICCARRE blogger: the only known mention on better than 1/7!

Dixit Leibowitch:

They dreamed of it, Charles-Edouard did it!

The Eclipse lasts ... from 7 to 35 (*) j ... Thus ...

# intake  1 / X   VL   1 7   <20   2 9 3 9 4 9 5 9 6 9 7 9 8 11   <20   9 11 10 11 11 11   <20   12 11 13 11 14 12   <20   15 11 16 11   <20   17 14 18 13   <20   19 14 20 15   <20   21 14 22 14   <20   23 14 24 14 25 15   <20   26 16 27 17   <20   28 17 29 19   <20   30 22   <20   31 20 32 22   <20   33 27 20<VL<200

Obviously, protocolization implies that we limit ourselves to 1/7 ... Yes, but Leibowitch's recipe is a MOAB (mother of all bombs)! And it works wonders. When one is in the right alignment of stars, that one is not bound to the injunctions of the Master, that one writes regularly on 4/7, 1/7, well, one asks necessarily the question: what about beyond 1/7: Exactly as Leibowitch evoked it; 2 or 1/10, then on 14, etc ... We will go to look for the limits of our own system, and then adjust. Its miracle is the Eclipse He or She, infedded or not even concerned, does not rule: the Virus is the sole decider, it rules as an absolute master, and its miracle is the Eclipse! As long as the Virus does not go up, it does not go up: it's just as simple as that. There is no known reliable predictor, not even proviral DNA as demonstrated, conversely, CHUN in Toronto: moreover we don't give a damn: you measure the Eclipse, then YOU decide. The table opposite is my ICCARRE schedule beyond 1/7, with 1/X going on, without the slightest blip, up to 1/22, easy... Beyond, at 1/27, it trips... Fine ... We make a note... The 190 eligible and observing patients have ZERO intrinsic failures at 4/7, and now we quibble to launch the QUATUOR trial! With this experiment, I learned a lot... In retrospect, I should have done an analytical interruption, with a weekly step: Ananworanich tells us that the average is at approx. 21 j. (*): I'm just an average patient! Nothing special! And this was before Dolutegravir (Tivicay ®) arrival which opens new horizons.

Well ... So when I 'm being told that I'm in tow behind Leibowitch, it makes me smile ... This is no beauty contest. It is a strategy based on observable facts: I have an eclipse of a little less than a month, so I set the cursor at 15 days.

With the good old patent, I made almost an entire year at 1/14 and better, just count the days on the table ;-)

I passed the 6 months beacon with the wonderful Tivicay® 50mg + 3TC 300mg: 5 months on Sat. + Sun and 1 month on Sundays, double dose: always <20!

We are May 1st and I try again at 1/15, ie, Remission-24 (I will explain ...) with a whole new method.

What to do with the advice of good old Pr. Péronne, who orders to wait for the end of that trial, then for the next one, and then whatever else? I plug them where they deserve to be!

Happy MayDay, good fuck, and not too many meds! OK?


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