Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - 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 ...)

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

Dolutegravir, R263K and DOLUMONO

By Charles Edouard!

Pr. Philippe EVEN: Each clinical trial is a detective novel, it is first a novel because it is false, and, it takes a detective mind to detect all maneuvers.

At the min. 53:30 of the Even video.

In order to better understand this post, please read again DTG and R263Kand R263K and Darwinian sink

R263K is beneficial, it amplifies the effect of Dolutegravir, and can even explain an Absolutegravir-like effect. This is a beneficial mutation, which is not the stepstone to others.

It is also beneficial to the reservoir (post to come). And it is, at most, commensal of the VL decay. When the pharmacological pressure is lowered, if it is there, well ... As the rats leave the ship, it comes out first ... Even if it quickly becomes invisible, drowned by the fittest virus (the original one).

In the table, a patient is identified with R263K; The authors, by their decision to stop the trial, consider that R263K appears, in a way, say, of a random event, and creates the VL raise: it would be the cause. This is consistent with the idea that the R263K mutant shows resistance to DTG. However, this resistance is very very modest, hardly measurable, and is accompanied by a significant loss of fitness. And also, why does it appear now, after more than a year ?? ...

Ah! They have an explanation: the dose of DTG was lowered by malabsorption: Probably suboptimal gastrointestinal uptake of DTG during 10 days due to gastro-enteritis

Here is our alternative scenario, more credible:

The patient has a gastroenteritis, takes none or little or inefficiently, the medication pressure decreases ... Dosage at 13h is 0.7, ie as my mini-Dolu, so, as expected, the virus takes up, with its commensal R263K, as a signature, not as a cause. Hazard of things, it is seen at this time: what happens if the situation persists: the virus continues its raise, the wild-type (or historical) virus, fitter, overcomes, very quickly, and the R263K fades out, relatively to it: it will become invisible. No visible mutation and a virus on the rise, but not too much... Does it remind you of anything? Look at the table...

In mono-DTG, to optimize the bioavailability, one takes with a meal. As for myself, I also break the pill between the teeth: broken, it disolves better.

Elementary, my dear Watson! Elementary???

The event does not arrive stochastically (randomly in time) at week 60, it arrives with ... the winter and gastroenteritis! Bravo!! The authors have just invented the rain! Well, that's too sad!

There you have it! All ? Absolutely everything ?? All ???

Oh really? The virus goes up with its commensal R263K, along with an accidental drop in drug pressure ... Certainly ... But was it doing there in the first place?!

It is the summer, we take our time: it will be for a next post! It's fun, isn't it?

In the news: DTG + 3TC, in first line, <500.000 and an overwhelming VICTORY

B. Taiwo presented the results, at S24, of ACTG A5353: phase II DTG + 3TC, in first line. It is a little more ambitious than PADDLE (20 patients under 20.000 copies), but less than Lanzafame (20 patients <100.000 copies, in Mono-DTG, with selected patients).

IAS-2017: the consecration of 4/7

For the ICCARRE session, the conference room was full and many screens had to be installed outside. Standing ovation at the evocation of Leibowitch (ICCARRE), a sought-after participant, adulated, congratulated and even rewarded: the victory was such, that we will make a jubilatory post, at back to school! , that was sooo enjoyable

Tiring but victorious week: Good Weekend and good fuck

Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - 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 ...)

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

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

Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - 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 ...)

R263K and Darwinian Sink

By Charles-Edouard!

Here is a testimonial DTG 100mg / week ...

With Dolutegravir, as a monotherapy, we have opened the Pandora's box: some will not get there (eg DOMONO), others will get there (eg DOMONO, again), and even go further in aleviation! There must be a limit ... How far can we go?

Dolutegravir and the Hybrid Behavior

It is difficult to understand: mono-DTG has given excellent results in many patients, and some discordant results, including, in DOMONO, a patient with a surge at 70,000 copies, without mutations, and with, so we are told, a good adherence: it is hard to believe!

For some, DTG is an Absolutegravir, for others, it's just a powerful ARV, no more. Absolutegravir has a unique mode of operation: it never give resistance. Dolutegravir presents this mode (pseudo-Absolutegravir) for some, and commonplace ARV for others...

The Darwinian well separates 2 modes

Whenever the Darwinian sink separates the two modes, there is an Absolutegravir side and a trivial side.

The maintenance patient can either maintain maintenance, stay at the starting point or even drop his virus into the Darwinian sink (orange path) or fail with a mutated virus (green path) or even a non-mutated virus (in appearance) (red path).

There are therefore 3 types of results (and not 2): maintenance (or even improvement) of the control, escape without mutation, escape with mutation.

Let us keep this pattern in mind: we will see scientists and clinicians throwing at each other okases and anathemas, to the great detriment of patients and the benefit of Big Pharma, with usual useful idiots as a megaphone.

Dolutegravir, R263K and Darwinian sink

Dolutegravir HIV tivicay resistance R263K HIV darwin mutation reservoir cure The naïve patient, having a virus, as wild as possible, has everything to succeed his/her attack treatment, in mono-DTG. For now 100% success at Lanzafame: he has an Absolutegravir.

One raises the pharmaceutical pressure: the virus descends, without mutating or even mutes (R263K) to fall into the sink.

If one reduces the pharmaceutical pressure, the virus goes up, exhibiting, for a while, a R263K mutation (possibly), and if one lets go, it goes up further, and the mutation might become invisible (while remaining present? )

The well, the 3 zones and DOMONO

Now that we have more baggage, we can get to DOMONO. An intermediate presentation of DOMONO is available here (presentation at Glasgow 2016), the poster with conclusions was presented at CROI-2017. You can take a step ahead of our summer series, by identifying the 3 areas of results: success, failure without resistance, failure with resistance. Our next episode: Is a failure with the R263K a resistive failure?

This story is rather complex (I simplified a lot ...). You may want to read:
Monotherapy with either dolutegravir [...] in humanized mice (you have to read the complete article to see that the failing mouse was underdosed, otherwise it is misunderstood).

Wainberg and Mesplede explain that the R263K trick may not work in 1-10% of patients: Polymorphic substitution E157Q in integrase increases R263K-mediated DTG resistance

The Achilles Heel is well detailed by Dr. José Moreira in Dolutegravir monotherapy as a simplified strategy in virologically suppressed HIV-1-infected patients.

Patient selection will be crucial

Careful patient selection will be an important aspect for mono-DTG (attack or maintenance). To note this Saturday 22 July the conference: Global HIV Clinical Forum on Integrase Inhibitors (sponsor ViiV Healthcare ...) with a program denser, in fact, than the one published.

Good ... Work in progress ...

Good Week-End and Good Fuck!



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

Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - 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 ...)

IAS-2017-Paris, ANRS-4D

Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - 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 ...)

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

IAS-2017 in Paris, ANRS-4D and 4/7

By Charles-Edouard!

After Durban (2016), Paris hosts the IAS-2017 congress. A trimmed, more scientific edition!

ANRS is a co-organizer. Its only relevant contribution to history was ANRS-4D: the rest is of no interest, others would have done anyway, or appaling fiascos (eg Mobidip or Ipergay, so quickly forgotten). ANRS-4D, as an unfinished version, was presented at DURBAN.

There will be an ANRS-4D poster, announced as: MOPEB0321, ie Monday (MOnday) Poster Exhibit session B; details are not yet available.

It is not very much, but apparently they had to struggled quite a bit to get something!

IAS-2017: alleviation session

There is a session devoted to alleviation:

Professor Katlama will talk about initiations under mono and bitherapies, normal ...

Dr. Pedro Cahn, bitherapies (father of GARDEL and PADDLE), normal, a Thai doctor of reduction, good, why not ...

For strategies 4/7, there will be ... Discussed by Dr. ... Discussed by Dr. Molina Anna Turkova !!! Paris will discover her. Unknown? She is coordinator and author in the BREATHER trial (5/7), her topic is: Treatment four days a week: for whom is it an suitable option

She may not be aware of ANRS-4D: even the press release has disappeared from ANRS site (see a back-up here)! Has she gained experience on the 4/7 somehow ??? (Or Penta-15?)

The situation in the fields has changed quite rapidly:

In Garches, data are collected from 114 patients (FASEB J, 2010 and 2015): no failure over more than 600 years of treatment in 4/7.

ANRS-162-4D, enrolled 100 patients (see IAS 2016, Durban, manuscript submitted for publication): no failure in eligible patients who adhered strictly to the protocol, ie, zero intrinsic failure.

As of November 2016, French Guidelines, quoting BREATHER and ANRS-4D, authorized the free practice of 4/7, outside of clinical trials.

In addition, 2 patient associations collect clinical data, in parallel and independently, from conventional clinical trials. A list of doctors is available.

Today, patients under treatment 4/7, in France, can be estimated at about 500 ... And counting! Paris follows trendy fashions !

A large, controlled clinical trial, ANRS-170-Quatuor, will soon begin in 62 French university hospitals, with 640 eligible volunteers.

It can be anticipated that this presentation, at IAS-2017 in Paris, will have a significant impact on participants ...

Has she had a chance, at least, to discuss this with investigators involved?

Breather: a good trial, a bad theory

I have echoed BREATHER, here, in details! This is the only place.
Unfortunately, the authors theorize, speculate, wrongly. The weakness of the authors of BREATHER is to theorize around a pharmacokinetic specificity of EFV (whereas the majority of children take AZT, with a short half-life ) There are reservations here, and there, that have been added by castrators, on a very undefendable argument. It is a shame because it deprives hundreds of thousands of children of a salutary strategy. I would like to remind you of a fundamental difference between BREATHER and ICCARRE / ANRS-4D / Quatuor: the lack of prognosis on genotype!

4/7: for whom is this a suitable option?

The question is interesting and falls right to the point: we will listen to the arguments of the restrictive clan, and dissect them! Remember to record the arguments of this session.

It was a tiring week! So, Good Weekend and good fuck!

Comments

Anonymous 15 Aug 2017


Charles-Edouard! 15 Aug 2017

Summer 2016: we offered a serial: ANRS-4D and the cheaters Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - 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 ...)

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

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

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

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.

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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