184

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



Mono-Cabotegravir: it makes sense!

By Charles-Edouard!

Read right here, in the discussion ...

Knock on wood... That is to say, hoping that it will hold up against all odds? At the beginning, in 6/7, I was a bit nervous. Knowing where The Monster is, at D+27 in my case, knowing if he has a reservoir lair), disappeared in my case, it helps to live confidently, without even touching wood. We can consider 2 approaches: Eclipsotherapy (measuring the Eclipse, then adjusting the tempo, or cautious advance, under frequent CV, at the beginning, starting with 2/8... This is how I discovered my new mode...

The Right Dose: a promise never kept

Overdosing does not happen by chance: it is imposed, among other things, by the emergency. ARVs, when combined, can do more than add up. By synergy, 1+1 = 3 or 4 or...10. Synergy will apply to A+B (e.g. HCQ+AT), but not to A+X. The Zotorities, (in fact, only the FDA counts) were considering an adapted dosage, reflecting the synergy. That's good, that's legitimate, but in a hurry... The pressure was on for a "let's see what happens next".

It's understandable. The promise is legitimate... The labs are doing their jobs, each one on its side, proposing the maximum dose, without even trying to position themselves on an optimum of efficiency, cf RAL, EFV, and so on, the Zotorités have done theirs: authorize, and behind... Behind... The medical profession is absent! Patients you have been betrayed! Betrayed by whom? The medical profession which has failed to keep its promise and its self-proclaimed deontology of not doing (too much) harm!

They did not do the job! Period! Some of them have tried a little, the Fauci, Leibowtich, Katalama, A. Calmi, with more or less intelligence and more or less perseverance. The associations have seen their members change, the initial pugnacity is lost: nobody cares and the victim is you! Doubly... Firstly because the overdose is never a plus in terms of health, and also because the billion Euros thrown out of the window, it is as many relocations, unemployment and social suffering!

Overdosing: EFV, NVP, RAL and the ultimate... DTG

In a famous article, A. Calmi gives some historical examples. Alaxandra, why stop in such a good way? Why offer the dosage only to patients who do not tolerate it well, as if toxicity was limited to intolerability.

The most devastating drug is Efavirenz. First, because its tolerability is so poor. Secondly, because the shameless dose of 600 mg has finally been replaced by 400 mg (see WHO). Ah yes... Replaced in the USA and in countries that depend on American aid... Yes, today we have better combos in Kinshasa than in Paris. It's to die of overdose! Finally, because the phase 2 trial did indicate 200 mg as the dose to be retained. Even worse, this trial, which is supposed to protect against overdose, was done at 200, 400 and 600 mg. 200 mg was the lowest dose tested. So to know the dose to be retained, it would have been necessary to (re)test lower. A theoretically favorable value is ... 60 mg (in combination with TDF/F-3TC), but it has not been tested!

RAL is a real galenic disaster: the manufacturer is on its third galenization! In the UK, the reference treatment is RAL 1200 mg + ABC 600 mg + 3TC 300 mg, PER DAY! It's crazy! And people are taking it! Without question ???

NVP is a lot of nonsense! Even in Bichat (Peytavin ?) we realized it! That's how obvious it is! The bioavailability of the prolonged form (XR, in 1 tablet) is such that the dose in fine is 4 times less than the ANRS threshold dose, and it works. This dose is reached with a single standard 200 mg tablet. The ANRS threshold dose has not been corrected for this. So we have publications with NVP 200 mg + 3TC 300 mg, without concern. Note that patients who take 400 mg embedded in a plastic foam only receive 200 mg, so they do not realize it but their dose has been reduced de facto. The fact remains that this drug is too expensive and moreover it is not beautiful to see!

The worst of the worst is DTG: 15 times the IC90! Only that!

DTG is overdosed: CTG is the proof

The FDA distinguishes 3 types of patients: the newcomers(the naive, so aptly named), the experienced(yes, yes, they do participate in full-scale experiments) in success, the experienced in failure: If we propose a pharmaceutical formulation to these patients in despair, it is the MA assured, without discussion. This is normal. For the latter, it is 100 mg/d. Well... let's not quibble, that's the dose used for rescue, in a perilous situation. At the usual rate of ... 1200 Eu/month, it is classic, shocking but classic. The others? Well, it's less. But not less turnover, right? I'm a big Pharma who just saved your ass, so be nice. 600 Eu/month is the usual rate. And by simple rule of three, for 600 Eu/month, you will get 50 mg. Is it useless? But we don't care: we have to save ViiV from bankruptcy (all their drugs are in the public domain).

So we give 50 mg to people who don't need it. Who doesn't need it? People who have a susceptible virus? Who is susceptible to a susceptible virus? People who are genotyped seriously (or even phenotyped) and people who are successful. So, in these people, yes! we can lower the dose, even to the reasonably acceptable dose in the phase 2 trial, i.e. 10 mg of DTG. But we, the chemists stuffed with $$, have something better! We will give you the same corkscrewbut change the handle. We change the name, the thing, we redo the studies, we drown the fish poison and... We change the dose(of the same corkscrew)... And... The target population.

We fire the Trojan horse, the failed patients, the few who have allowed us to stuff the whole planet, and us (in $$) at the same time. Read the HAS, here: right on target:
In these patients, 50 mg DTG is 15 times (15 times!!!) the IC90. With CTG, at 30 mg, it will be 2 times less corkscrew (technically we say pharmacore), that is 7 times the IC90 . And it is indeed the ideal IC90, since we have selected the susceptible patients. So even 30 mg seems huge!

Mono-DTG works on susceptible viruses and serious patients

There is a wonderful Swiss trial with 100% success (try to do better!). Lanzafame published its results on patients, without too restrictive screening, it also works if you follow the protocol well. Once people have proven that the virus is not twisted and that they know how to follow the protocol, one wonders why on earth they should stay at 50 mg!

I did Mono-DTG 1/2 pill (6 months) then Mono-DTG 1/4 pill (6 months), in 7/7, with no worries, no failure, no resistance acquired, nothing, Nada. To me, I should not be offered VOCABRIA... With my experience of Mono-DTG 12,5 mg (7/7), I will always go for MONO-CTG 7/7, just for fun.

Mono-CTG injection: it looks good...

Good compliance is key to success with Mono. And what better way to measure and guarantee compliance than with injections? It is not easy to hide or minimize non-adherence with injections... So, then... Well, that's for another time! Subscribe now!

The orphan virus is making babies

- Will mass vaccination, with a mono-centric strategy, prove to be a big mistake? I doubt that history will ever judge it. The West has been living for 2000 years in a macabre, obsolete hysteria... And the inventory of this millennial error is still pending. Is vaccination reversible? In general, no... For a real vaccine, it is not... But here? Antibodies have a limited lifespan, it is a chance to seize! Also if your virus acquires resistance, you have the choice (if you are allowed to...) between overdosing and drowning. You have to make a choice and beware of resistance breeders. While we can, drowning is my strategy of last resort. Sonigo has been explaining for a long time that from evolution to evolution, the virus should become more contagious AND less virulent. P. Sonigo gave an excellent interview. Geert Vanden Bossche explains here, in French, that the succession of waves indeed favors contagiousness, but that there is no apodictic necessity for less virulence. I had said, at the beginning, that a selective strategy of Covidization of the youngest would be possible. Now on the table: omicronization of the injected...

The false witnesses and their obliged accomplices

Francis Palombi will have admitted having deceived the journalists of BFM, at the time of a shooting at the hospital of Neuilly Ambroise Pare. Caught red-handed, he declares: Bad comedian certainly. Sincere at least. I assume my convictions. Did BFM let itself be trapped? Or has seized the opportunity to stage the convictions of... BFM. The debate on intermittence will have been polluted by false testimonies AND those who allowed them. This is important: the responsibility of the false witnesses exists, but the responsibility of the media who carry an intention, even a conviction, is even greater.

In the news

- I had pointed out Fenton's post, here is the interview he gave (and which disappeared quickly...). Beyond this controversy, his blog addresses a very interesting issue: the assessment of risk by the Bayesian method

- two articles of great importance for us: A possible sterilizing treatment for HIV-1 infection without stem cell transplantation and Distinct mechanisms of long-term virological control in two HIV-infected individuals

- Links disappear with time... My new MegaArchive keeps this blog in-extenso as well as all the resources, including video: nothing will be lost anymore...

- Happy Holidays !!!

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Turn off the TV and don't be fooled by the Parisian venality

183

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

A giant step towards recovery and that's me!

By Charles-Edouard!

My tank has disappeared... or... did I make my tank disappear?

As long as you give a prize (INSERM) or a lot of $$, it would be nice to do it for a real real ization. And, to give to those who do. Not to the spectators! The spectators watch, amazed, admire and... Applaud!

Without further ado I reveal where I stand, and we discuss it afterwards. My tank is measured every year: 2015, 2016, ... 2018. Low but present, unequivocal. 2019 and 2020: three attempts where the lab said they were unable to do the measurement. 2021: the laboratory confirms the undetectability: it is without appeal: something happened!

And this something is huge: the disappearance of the tankit's gone under the radar! Now, if you find even one doctor capable of showing such a masterful Before-After, just let me know: I have never seen one: it is the GRAAL of the grail: no one has ever managed to do it, except by genetically modifying the individual and perhaps in the Biosantech trial (to be verified...). You know how to do this, you are part of the Kador, the STARS. And if you don't know how, well, you are not a STAR.

We are talking about DNA(measurement of the reservoir according to the ANRS method) and not RNA(whose undetectability is maintained by the ICCARRE+ method)

Under the radar! it is under the radar...

When the numbers are low, the validity of the results is questionable... Yes, yes, yes... And we'll do it again in 2022(if this stupidity of sanitary pass has ended, if not, we'll do it later, or elsewhere... ). I'm not worried or in a hurry... from 2015 to 2018, the lab was able to come out with results, but not in 2019 (twice...) we suspected something! Again in 2020... These are background noise problems: the signal is drowned in a small hubbub. So for 2021, I used a little trick (that I got from Ananworanwich) to try to get the signal back to the best I could dream of. Who knows... But at least the machine spit out something! It spit out ZéRo, and that's not nothing!

When does it go under the radar?

Good question... First, when it was above the radar, it was for real. How do we know? because several months before the last 'positive' reading, I had a (very) high RNA reading (at that level of CV, it's not a blip!). This virological failure, frankly, will have been recovered with brilliance, and above all, a few months after the incident, the reservoir was as usual, in conformity with the classical observation that a short period under active viremia does not affect the reservoir level.

So moving the tank, one way or the other, is no small feat! You make a controlled slip and it doesn't change your burden. The alla Pharisee argument that intermittency (or even failure) would make the tank go up (boo!...) is at odds with what we know. There is no need to worry unnecessarily...

I think that the passage under the radar dates from 2019, and that 2021 is only a confirmation. Besides, after 3 unsuccessful readings, we could have already ruled. And all these impossible or null measures, are in a series that starts in 2019 and interrupts an earlier series of remarkable consistency!

No more reservoir? What's the point? What to do next?

As long as you have a tank left, there are a lot of questions that don't arise! Nobody asks them... And when you don't have a tank anymore, everything comes up: you are in terra incognita! So, we'll see about that next time

Obligation of treatment / Judiciarization

When a virus comes from nowhere and appears 800 m from the only laboratory in the world working on these living viruses, we say that a pangolin has been killed by a bat. When a variant appears without any known recent emergence (despite 2 million genotypes!) we immediately find the source: an S+ patient with uncontrolled HIV... Oh well... The use of some mutagenic molecule? No ? Really? No? Well... If you say so. Of course, there were some who immediately decried the situation and wished it would end: hear, hear !

In the news

- Raoult said he reviewed a forthcoming article on a very large prophylaxis study at HCQ... Hi... Hi... He knows the result... Do you? Not yet... He seems quite confident about the future, don't you think?

- In the meantime, a large prophylaxis study with VMI confirms, not surprisingly, that it has a role to play!

- Merck announces that it has stopped its Islatravir study in 1/7, under a pretext as futile as it is unverifiable. Let's keep an eye on Merck's next announcements on Islatravir. I bet that they did not hang up their apron and that the others finally gave in in the negotiations... Merck's initial objective was always injectable. The oral form in 1/7 was only for as long as there was no injectable solution... And if the injectable that we feel is coming does not work, there will always be time to come back to 1/7, but in IRT, this time, as it would have been reasonable to do from the start... We'll see... The saga continues, and we will come back to it.

- bad luck: Pasteur (Lille) interrupts its clinical trial... For lack of patients! In the middle of the e-ieme wave! You have to do it!!! it's here. By dint of being soaped the board, it wears out!(Even Pasteur... Apart from laying down algorithmic elucubrations that leave one quite perplexed...)

- Pr S. Gayet is an infectiologist who seems to deal with nosocomial diseases in hospitals (of which Covid is a part...). Behind his phlegm and his Alsatian accent, he says exactly the same thing as Raoult. It is less brilliant, less striking, but it is kif and it is here.

- A stellar article by Norman Fenton, who notes a wave of deaths, NOT Covid, among NON-vaccinated people, coinciding with the (NON)vaccination campaign, whereas this campaign is, for them, a NON-event! The (non covid) deaths of the freshly vaccinated (side effect: death...) have been attributed... to the cohort of the ... NON-vaccinated. So, of course, when you correct the bias, it looks bad. It's a bit hard to read and it's here.

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I'm walking against the current, because I don't know how to walk against my heart...

182

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

Islatravir: a remarkable persistence

By Charles-Edouard!

The dilemma of injectables:

In a somewhat rommed vision of the role of historical associations (e.g. Act Up), we see activists struggling with a criticism, sometimes relevant, of therapies. But, for years, none of that! Some declare:
Les ActupienNEs, an association where expertise is our weapon to fight against AIDS in the face of the authorities and the current under-information. (sic)
If you are not funded, you run out of money quickly, and if you are, you shut up! Injectables, as attractive as they are, are a real massacre: overdosing at its peak. And no one, no one to ask the slightest question... That's how it is...

Islatravir and persistence: Stage 3 of development

This ticket is crucial for the future! We must understand the implications... In our previous posts, here and there, we had followed the 'classic' development aiming to gain in efficiency and lose in toxicity. Well... It was funny, but well... An inefficient or toxic molecule would not find a buyer today. So, the gain of efficiency or the loss of toxicity, it's good but it's not likely to move in the houses. With step 3, we're approaching what is so specific to Islatravir, which means that we'll be able to do intermittent treatment more comfortably, but we'll also have to do it: no escape! So, it is important to follow up!

The toxicity of metabolites

The problem of intracellular metabolites: Degradation of nucleobases leads to loss of biological activity of nucleosides and sometimes free nucleobases are toxic. It is therefore desirable that the glycosylated bonds of nucleoside drugs are stable in vivo.

As expected, 4′SdN showed strong activity against all existing resistant HIV strains.

Next, metabolite toxicity was tested in mice. The 2-aminoadenine (EAdA) and guanine (EdG) forms were highly toxic. Degradation by adenosine deaminase is a serious problem in the development of antiviral nucleoside drugs. The researchers finally recognized that 4′SdN (candidate in the previous step) was not a good solution due to its toxicity (metabolites) .

However the 3′-OH group is essential to prevent the emergence of resistant HIV. Different variants have been created: EFdA, EFddA, EFd4A, ECldA... EFddA, EFd4A and Ed4T, d4T, which do not have a 3'-OH group, were effective against wild-type HIV but decreased in activity against resistant HIV. On the other hand, EFdA and ECldA, which have a 3'-OH group, showed excellent anti-HIV activity against wild-type and resistant HIV. In addition, these selectivity indices (the ratio of the toxic dose to the effective dose) were greater than 100,000. This result indicates that one can have both the presence of 3'-OH groups and low toxicity.

It should be kept in mind that in these inhibitors, the original form but especially the tri-phosphate form are active (cf Tenovofir, Abacavir, etc)

EFdA and its triphosphate form, EFdAtriP, are not a substrate of DNA polymerase (no toxicity there...). EFdA is therefore not toxic. The half-life of EFdAtriP in plasma was 17 hours in vitro, but more than 100 hours in vivo, which indicates that EFdAtriP is very stable and remains active in vivo: this indicates that RT also uses the phosphate form, EFdAtriP, as a substrate in vivo. This is the Kiss-Cool effect!

A new mechanism, therefore a new class

The EFdA is now well away from its ancestor, with its sulphurous reputation. We'll see later who this clunky ancestor is and quickly retracted by the marketing teams, who jumped on the observation that EFdA is a translocation-defective RT inhibitor that cannot move from its initial binding position to the next substrate-accepting position because the binding to RT through its 3′-OH and 4′-ethynyl groups is so strong. This is a defective RT inhibitor by translocation. Whew!

(Bah... If you figured that out, hats off!)

No intracellular degradation, in vivo

The trick is there! Once in the cell, Islatravir is metabolized very slowly, the metabolite, itself active, is also metabolyzed very slowly. In a word, it persists ad vitam, so to speak. And who is the good model of an ad vitam persistent inhibitor? Lead (and other heavy metals). If we are not careful, we can reasonably ask ourselves the question of 'lead poisoning' with Islatravir. There would then be a real problem of cumulative dose, which, in the long run, could bring back the toxicities of its infamous ancestor. For the moment, according to the designers, this would not be the case... But it's always the same story!

We will follow with attention how Merck's marketing services could try to hide this, by planting a forest of arguities around this jewel. It started with the idea of selling Islatravir at a dose of 0.75 mg. Now the project is at 20 mg. That suits us... As I said before, I don 't see how Merck will be able to sell this e-th ARV without promoting its only distinctive advantage: persistence!

Weekly intake and 1/15

In fact, the weekly (or even better) oral intake is the objective enemy of the treatment obligation... You may not have realized it, but those who are obsessed with the injection do...

Obligation of treatment / Judiciarization

I guess now everyone understands that the pass, supposedly yours, is in fact remotely disengageable... It's freedom conditioned to the goodwill of whoever runs the central servers. Brrr... We'll have to take refuge in the bush. It's pretty awful, when you think about it.

In the news

- The doctor who made this video is very British... If you can live with it, it is a very clear explanation of the difference between the new Pfizer drug and IVT: New Pfizer drug and ivermectin

- A clarification from D. Raoult on confidentiality in HIV: it concerns us all and it becomes problematic. On this Video, at minute 7:30 We will come back to this, it is really important!

The French genius

This old tune is haunting, we all know it, it comes to us from past times and ballads us: Mon amant de la Saint Jean...

More subtle is this extraordinary film of Jean Cocteau: Le Testament d'Orphée or don't ask me why... You can find the complete version on DailyMotion. It is bizarre, at the limit of understanding, and also very French! very! The Chinese version makes no sense. You can listen again to the magnificent Danse des ombres heureuses (here, Rampal on youtube), extracted from Orpheus. This revolutionary work will trigger a new quarrel after the famous one called "des Bouffons" (which opposed Rameau and Rousseau). Here the partisans of the French operas, the "Gluckists" and those of the Italian opera, the "Piccinists" will clash.

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

181

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

DTG: a failure without induced resistance

By Charles-Edouard!

DTG: did my failure create resistance?

For those of you following along, I failed a lot of copies, a lot! Plus, it was maybe the only time I was behind on my resume schedule. I did it at 3 months, instead of 1 in the exploratory phase. That's how it is, sometimes I get stuck abroad, without access to the CV, or to the meds for that matter, hence the interest of the 1/X: you leave with a few weeks of treatment, but you stay for months (and months...), it's all good! Well, I did what I shouldn't do. Leibowitch said it again and again: you have to make your CVs(in the exploratory phase, of course).

Even if I was late, I did it... I was on DTG monotherapy, 150 mg in 1/7 (collated in a capsule, which is perhaps the problem). Well... The failure was only a half surprise. The height of the failure was a real surprise! I blew up my counter, and I think I even made the highest failure of all I read in Mono-DTG, that's saying something!

Damn, didn't I create some resistance?

Catching up with the DTG

Even Leibo didn't have much of an idea on the subject... However, I knew one thing, on the Integrase, my virus is clean! It's not complicated, it has never seen RAL (let alone EVG, I'm not that stupid). So, for me DTG would act like an Absolutegravir, a concept I developed, not tested, except that here it is the truth.

Understanding that viruses that have been exposed to old INIs (RAL, EVG) are likely to acquire new resistances under monoDTG is the Achilles heel of this strategy. On the contrary, when we look at the rare French publications on DTG resistance, we identify multi-resistant patients (INIs) included in the rescue trials. I have not seen any published resistance on originally clean viruses. In other words, de novo resistance on non-pre-exposed virus does not exist! And if you find any, please correct me.

This is very important because it is the cause of the extraordinary overdose of susceptible patients because the choice of the dose was guided by the dose needed for mutated viruses. In a word, thousands of patients are being overdosed with DTG (and soon injecting themselves) at a dose chosen to control the virus of the few who had messed up with the virus: you don't treat your virus, you treat someone else's.

For me, DTG was an Absolutegravir... So, if my vision of what is an Absolutegravir is right, this is the opportunity to try it! Leibo proposed a drowning. I decided to try resuppression with DTG, there would be time to do a drowning, if needed, later on. I have already explained the chosen scheme: I resuppressed with DTG, without making a resistance profile, assisted by usual and less usual companions: it worked like a charm. In 1 month it was fixed, as usual for DTG, so no damage... So DTG is still part of my world.

Has DTG remained an Absolutegravir?

If you failed Mono-DTG, you might be afraid that this wonderful property (Absolutegravir) is now a thing of the past... In Eclipsotherapy on Dodeca, we don't really care. But then again... If DTG is amputated, we might as well take it off Dodeca... The resistance profile, was not done, I resuppressed without worries, so basta!

Except that... The Lab got mixed up with the brushes! Yes, yes... It happens! They did a genotype in addition to the DNA quantification. Well... I don't have a lot of confidence in these explorations at the limits, but well... They did it, they did it

Well yes! No resistance mutations in the INI

That's it... that's what I thought! My virus stayed clean (at least what the lab says). I was a little suspicious, but it's reassuring to know that! You're doing great in Mono, and, you're still perfectly susceptible! DTG is great for those who know how to use it! And to use it alone! I was very careful not to associate it with 3TC, because the 184, you get it every time. But we're clean there too!

And elsewhere? I did 4/7, 2/7, 1/7, 1/15, 1/21, failed 1/27, Mono-DTG 25 mg 7/7, 12 mg 7/7, 150 mg 1/7 (failed) and nothing. Nothing from nothing... Not a single acquired mutation... Nowhere

In the exploratory phase, you have to make your CV!

Well... I didn't stay on Mono-DTG for long, so that must help a little. Since then I do my CVs religiously, in the descent phase. In stabilized phase, no... No injections, no more blood tests, the less I see the 'specialist', the better I feel... She is nice, very nice... She's nice, but you won't get better with her

Icing on the cake: the disappearance of the tank

This allowed me to discover(fortuitously, but not that much...) the disappearance of the tank: my big topic of the moment.

The next step after the disappearance of the tank is... It is... for another time ;-)

In the news

- A vaccine injection that must be repeated every 6 months!?!? Hello Houston: There is a problem...

- Mr. Zureik answers the challenge (it would deserve the Canard Enchainé): As an answer we have seen better!

- Actually, it's quite simple, you read about what makes the soap merchants tick. It's often interesting! It makes them angry because it attacks their business! The Chinese with HCQ, the Indonesians with IVT, the downgraded with NVP, the Malagasy with their syrup, they must be laughing! A good real laugh is communicative, it is joy!
Pr Perronne probably had the wrong idea about the herbal tea... Molecules coming from Nature are always there and immune to prevarication.

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Science under finance is only ruin of the Man...

180

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

Intermittence and flu vaccine

By Charles-Edouard!

The Thai health system offers the best quality/price ratio, it is well known. ARVs are not subsidized and are affordable for the average tourist. And the trip is fun! The problem is the cost of Biktarvy: 58 Eu./month (in France, it is at least 10 times that!), while NVP/TDF/F-3TC is 19 Eu. / month. There are many testimonies of use in 2/7... It leaves one dreaming! The (anti-)French social security system is a burden on the gross salary and favors relocations...

The flu shot? Not for me this year

Before, I had no objection... That was before I read, under the pen of the excellent Pr. Montagnier, that repeated vaccination does not bring anything, especially if one has already had a few natural influenzas. I am one of those people who listen to our best Nobel Prize winner. Do you have anything better to propose ? Well... So I listen... So, I made a bad quote: vaccine every 5-6 years, not more. On the other hand, I am very careful about the pneumococcus. Everyone around me is up to date.

2020: a useless vaccine!

I let myself be convinced by the usual TV shopping and I took the flu shot in 2020, so as not to be confused with the other lisp. As a result, I took the shot the only year the flu did not circulate

Vaccine and HIV: beware of CV rebound

Yes, yes... I know it's fashionable to participate in social networks by advising the vaccine to S+. All the more easy as for this blind medical advice, the selective censorship lets it happen... Of course...

You can look up the references on Pubmeb, there is a plethora of articles that note a (temporary) rise in CV just after the flu vaccination. The patient who is monitoring her CV during the ICCARRIAN descent phase can therefore consider doing her CV BEFORE getting vaccinated (eventually): there is no point in panicking. I even pushed the envelope a bit further by going to the hospital to have my blood sample taken (yuck...) and by handing my vaccine box to the doctor on duty, who made a face but did it, not for free, but for free!

It's not a big deal, but as soon as you mention the risk of blip, you get lynched!

Well... I did the vaccine and no CV, it's just as well, since we're going to go easy on the CVs, now that the 1/15 is well secured...

In France, flu vaccination is recommended for people over 6 months old belonging to a group at risk of complications (people over 65 years old, people with severe asthma or chronic lung diseases, people with severe immune deficiency). I have not seen a blind recommendation for S+ in general

The 2022 vaccine is kif-kif 2021??

According to Wikipedia, the effectiveness is usually assessed by calculations and simulations (whose results depend a lot on the chosen hypotheses ). Someone will have to explain to me the effectiveness of the 2021 vaccine, a period when Influenza has not circulated at all! In a context where people were cautious, it did not circulate: caution works! About the flu...

Weekly intake and 1/15

In fact, it's confirmed, my tank is gone (in the blood...) Before even asking the question of what made this possible, the question of what to do in 2022 arises.
I have never seen in the literature a trial showing the disappearance of the reservoir, i.e. with a before/after, including in the 'cure' trials (except perhaps, to be checked, the one in Brazil, recently). In other words, this is new... I'm exploring... Of course, this is great: here is what the biologist says

Obligation of treatment / Judiciarization

... The injectables are coming... That's it!

In the news

- Injectables are coming (finally!): the commercial match will soon be Vocabria(2 big shots every 2 months) vs Islatravir(in 1/7 'official' and more if affinity). The Tele- BichatAchat will have a great time!

- I am now on Telegram: see the link https://t.me/charles_edouard

- Another excellent article: Should we vaccinate against PCR detection or against Covid-19 disease? by Pierre Sonigo, Caroline Petit, Nathalie Jane Arhel

- No impact of HIV on the consequences of SARS-Cov2, according to this article, except, perhaps, when CD4 is low...

- Actions Traitements has a new information booklet: L'allègement thérapeutique dans le traitement du VIH. Go there if you want... My Practical Guideis online since... 2014!

The French genius

Samson François plays Debussy... This is not German music, nor even European! (I don't know what that means...) Suite Bergamasque : Clair de lune

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The real insider tip is to know which doctor to go to...

179

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

Islatravir and safety

By Charles-Edouard!

As the HAS is struggling to rule, we sometimes read a lot of nonsense (anonymously, on the net):

Where on earth did this come from? The conditions for inclusion in ANRS-4D and QUATUOR are 1 year of certain virological success. The treatment starts with a horse dose (induction) followed, in case of success and stability, by a reduction. We do not start with a reduction of the dosage on the first day or the day before our own death! The undetectability must be reached and confirmed by a test at more than 6 months (cf rare cases, seen in the Gilead trial, for example, the load can be undetectable a first time, then rise again, it is Raffi who spoke about it, that is to say!), one leaves oneself a little margin, thus that leads to approximately 12 months after the first undetectability... It's simple: too early you lose the benefit of the induction, too late you lose years of unnecessary overmedication!

Islatravir, a development not very XXI century

In previous posts, we have seen how Dolutegravir marks a fundamental evolution in pharmaceutical chemistry and inhibitors in particular. We find this same modernity in the development of anti-SARS antivirals. The idea is simple and the most modern technology is beginning to make it possible. Inhibition is a key-lock system: the better a key fits the lock, the more efficient it is: it sticks as close as possible to the function and therefore prevents any other molecule from accessing the enzyme, i.e. the protein that catalyzes the reaction. No catalyst, no reaction. [As a reminder, in classical chemistry, an inhibitor is called a poison, of which the best-known example is... lead (as it screwed up the function of the catalytic pot, it was removed...)]

The modern method benefits from the latest advances in protein (including enzyme) imaging/mapping. It's long, it's complicated, but more or less we manage to make a 3D map, with a very high definition of the coastal profile, thus of the harbor which shelters the catalyst. It remains to design a Sardine that will block the port of Marseille. A lot of tools are needed, the map and docking software that calculates affinity, steric hindrance, etc.

There is a method and tools. So much so that it raises the question of 'discovery'. Indeed, the lock controls the key and there are not 2 perfect keys for the same lock! The one who presents an optimal key for the lock will obtain the patent, thus the exclusivity. However, he has only made the 'negative' of the card. The question then arises as to the fair remuneration of the person who has made... the card! Because the real discovery is the map, and the invention is its symbol(in the etymological sense of counterpart). And for a given map there is only one optimal pharmacore. This forbids any further invention! Dolutegravir marks a new generation of INI and also its end. The possible improvements, relative to this catalytic site, are marginal. It is therefore not surprising that Bictegravir(Gilead, actually Japan Tobacco, Tokyo) is the look-alike of Dolutegravir(GSK, actually Shionogi, Osaka): all this is drunk from the same glass of sake!

Well, Islatravir is just the opposite! It's a fin-de-siècle molecule, developed in the old way, and kept in a closet(yes, yes, this part is a bit painful to the heart, when you think about it), it's due to intuition, to experimentation, to expertise.

Islatravir: episode 2, safety

As we saw in a previous episode (read it absolutely), the starting point is a shitty ARV(we'll come back to that) which has been worked on to optimize the recognition. Great except that other enzymes recognize it too! It messes up the reverse transcriptase (what a bitch!) but also natural and useful polymerases. Shit!

Islatravir and... antibiotics

Many naturally isolated nucleoside antibiotics are available. Most of them have been modified with a physiological nucleoside, and although they have high antibacterial and antitumor activity, they were also very toxic and could not be used clinically (e.g. Tubercidin, Aristeromycin, Nucleocidin...). They were unusable... Therefore, in the 1960's and 1970's, nucleoside chemists chemically modified these antibiotics again on a single site in order to obtain nucleosides with a better biological activity.

However, once modified, the activity was lost in all cases. Dang!!! So, you're ticking your thing off at one point (or more), you eliminate the toxicity, but goodbye the efficacy��! Needless to say, by the turn of the 80's, no one was doing this anymore...

Thus, many researchers at that time left nucleoside chemistry, claiming that "nucleoside chemistry has no future" (especially in the United States, it became difficult to get research funding and the move was rapid). However, the Japanese researchers surmised that "loss of activity means loss of toxicity."

Loss of efficiency on the polymerase

The idea is the following. The problem is twofold: the selected molecule is efficient against Reverse Transcriptase(good) and Polymerase(not good). If we try to reduce the toxicity of the molecule/polymerase couple by the classical way (now abandoned) we will reduce the toxicity (towards Polymerase) and the efficiency (towards Polymerase), which is a good thing because it will reduce the toxicity due to the efficiency on Polymerase !

Therefore, if the toxicity of 4'SdN in which one of the physiological nucleosides is modified is high, it is considered that the toxicity can be reduced by modifying it further. This is because human nucleic acid polymerase recognizes our modified nucleoside (the candidate molecule) at one site (it attracts it as a docking port) and integrates it into the DNA or RNA, but it is expected that a nucleoside modified at two or more sites will not be recognized and will not attract it anymore!

That's it! Islatravir's ancestor has just lost his toxic virginity!

... Without losing its efficiency towards the reverse transcriptase. An efficient aegis, whose first descendants are non-toxic... And it is not finished! Researchers are going to work on the metabolism (the life span), because it is the objective: to make a cheaper ARV!

Well... We'll see this next time

The French genius: Sonigo and Raoult, always...

You have to read the best! The best modern and accessible microbiologist is Raoult, unless you have someone else to suggest, if you wish. Even if he is not involved in the problem of the moment, we must read and reread Sonigo. He predicted, on the basis of general considerations, that the virus would become less dangerous as it would inevitably mutate. Let's go for the general rule, and we'll see if the massive Spikisation comes or not to disturb the context. We will see... Remains that Raoult, he comes with marbles, genomes: the virus/variant cannot not mutate and its effect d��croit at the grè of successive mutations. There you have it... The usual future of a variant is to disappear, within about 2 months of its emergence. A whole new understanding of RNA virus epidemics is emerging to the public eye.

For the record, THE video of Raoult which dedicates this erosion is here. Erosion considered by Sonigo and quoted in my post here. Because it is necessary to read and re-read Sonigo! And we applaud the prescience in this issue of JDS, remarkable! The interview dates from ... 1996! it reads:

One will also read with interest the interview with Leibowitch, and in particular this
Why is this important? because it is the culmination of a series of posts to come on the responsibility of all (including patients) in overdosing. To be continued...

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Turn off the TV and don't be fooled by Pharisaical veracity

178

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

Lorgeril and his filly: a little science in a hysterical world

By Charles-Edouard!

Lorgeril and his filly: an already old observation

In the trial that paved the way for the marketing authorization of Genvoya(Gilead, again and again...) there is an annomaly, which, very appropriately, is resolved (by itself?) in the last stretch. I'm curious about this, but at the time I would never have questioned the solid science of double-blind trials. However, it was strange...

Is it possible to cheat a clinical trial? Normally not, but what about it? Once you open Pandora's box you find so many and more. The first one that made some noise was the Jupiter trial. The controversy continues (see BMJ article). And the valiant de Lorgeril, who put forward the cheating, will have been consigned to conspiracy, despite an impressive career (remember, the Lyon Study and the Mediterranean diet is him, among others). The denunciation of the Jupiter essay is here

So he has often discussed a bias in trials that seems to be on its way to being found in THE vaccination-that-is-not-a-vaccination...

Lorgeril and horse racing

His demonstration was brilliantly illustrated in a TV program that I did not find again. Too bad... It's still easy to visualize...

At the Grand Prix du Président de la République (yes, it would not be for sale, but it has a price...), the competitors are at the start. The favorite, Astra de Zeneca, makes a great start. She dominates! At the halfway point, her lead is clear: she wins, she wins! And it is the fall of her followers. The owner calls out to the judges: what's the point in continuing the massacre: for the sake of everyone, we might as well stop here and declare Astrée de Zeneca the winner, hands down. The public is all for the filly, favorite of the media.

The time to consult the Wise Men, which is, as we know, only a formality, Delta du Bengale comes from the end of the race and makes an unprecedented comeback. The outsider is relentlessly climbing back up and it is urgent to declare Astrée de Zeneca the winner.

It goes very fast and Delta du Bengale is neck and neck... Here she overtakes Astrée de Zeneca, beaten at the finish, to the great displeasure of Sir Zeizer, the owner

One must beware of a temporary superiority

The effect of statins is deceptive. They seem to be beneficial for a while, then the cardiovascular risk takes over. This is normal... In the end, everyone dies!

Obviously, the industrialist-sponsor of the trial has every interest in winning the decision at the most favorable moment! And to erase the traces of his misdeed. Out of compassion, the trial will be stopped in view of the obvious benefit (provisional, it is true) and we will even treat the control group in emergency. Oh the unfortunate ones who otherwise would have been victims of their abnegation: no more control group, no more remontada!!! And the trick is done!

Relative decline in the performance of genetic therapies

The hypothetical theater is being built in front of us: let the show begin! Israel, once shown as an unmistakable example, is turning into a fiasco... It's not yet sure, but it's taking the shape of a big increase of positive PCRs, for some or the others. Of course the pro-vaxx people look the other way. Yet Pfizer had negotiated with the Israeli government to have (and publish) the data, which they hoped would be unassailable.

Will Laurent Alexandre eat his hat?

A promise is a promise...

Obligation of treatment / Judiciarization

I had opened a section "Obligation of treatment / Judiciarization" concerning HIV... I kind of gave up because it's so hopeless! But well... Here we go straight to it!

The 1/15 / My tank

Well... Almost 2 years in 1/15 and an undetectable CV... I'm looking for my "missing tank" ... Well, not quite disappeared but it is confirmed that it went under the radar. That's good, it's confirmed! How much is it? We don't know more for the moment! I hear that people argue that as long as it hasn't disappeared entirely, there would be no benefit in reducing it to mini-mini... Really??? How many people do you know who measure their tank every year, make new arrangements and see it drop below the radar in less than 12 months? Leibo would have been thrilled as hell: It is nevertheless the strategy that he went to expose to Pasteur...

The French genius: Luc Montagnier

Me, I gladly listen to Montagnier... 4 pillars support Eclipsotherapy and 2 are perfectly predicted by Montagnier!(I will do a paper on this... )
A very good view of things in this Letter from Montagnier

1/ Coronaviruses in general are not dangerous.
2/ The SARS-COV2 Coronavirus has a natural origin which has been modified in a laboratory from which it came out. It is a pathogenic chimera.
3/ Both DNA and RNA viruses are made up of nitrogenous bases that belong to nucleotides.
4/ Variants are all the more frequent as vaccines become more widespread.
5/ The messenger RNA vaccines aim at producing a toxic antigen: the Spike protein.
6/ The fate of the virus
7/ Vaccinating during an epidemic period is a nonsense, increasing the undesirable effects: epidemiologists know it.
8/ Nature is stronger than scientists: collective immunity is a delusion.
9/ The health pass imposes quasi-mandatory vaccination to too many people, to avoid the responsibility of the government or the manufacturers.


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Turn off the TV/Twitter and don't be fooled by Pharisaical venerealism