128

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



The tenia and the denial of proof

By Charles-Edouard!

In the margin of a reckless hope for a vaccine:

DTG-25 mg (or even DTG-12 mg) is a much bigger loss than the 4/7 intermittence. Pharma doesn't want it? So what? We don't ask their opinion... Now, the doctors are something else. First of all, an infectious disease specialist is a low wage job: 35 Euros per consultation, that's 8 times less than a lawyer (350 Eu/hour). So if you do 1 consultation per year, instead of 2, well, it's a disaster, already that you don't earn much. PreP is 4 consultations/year, it's already better, and the guys are neither sick nor boring. So the problem is not the Pharma (overpaid) but the doctors, underpaid, but overestimated (since there has never been one to cure you...). That should make you modest!).

The Tenia and parasitic ideas

Ultra-sanitized, we know salmonella, legionella, tuberculosis and others only through the rare 'news'. Reading TREMPANO, one quickly understands that living in Senegal requires a top immune system. Not only is there a risk of catching these diseases, but also of dying from them! How stupid it is to believe that your risk is identical to that of people bombarded with pathogens!

So you probably don't know about tapeworms, those long tapeworms that cling to your intestine and feed on your food. You don't realize it right away. You can easily get rid of it with a deworming pill. It barely bothers you, and this tapeworm suffers the pangs of death, wiggles, lets go, and you find a long rubbery tube in the toilet bowl. Baptize it with the name of God, or of a pedophile Monsignor, before flushing it. By the way, baptizing your excrement is quite funny and salutary: it feels good.

Misconceptions are like tapeworms. They parasitize you, discreetly, and, once rid of them, you feel so much better that you want to shout it to the whole world. But there are places where people are religiously attached to them. Septism(the obsession to do 7/7) is a sacred parasite. If you don't revere it, don't expect to get your medical degree. Has anyone ever seen a poisoner's apprentice get his degree by checking the box 'cholesterol is innocent' or the box 'BCG is useless'? Those who had the right answer did not become doctors...

So, yes, I just compared sepsis to a condom for a small cock. Oh, but you are quite irreverent! Well, yes... A false idea, invalidated by experience, deserves no better than ridicule and contempt.

Septism, it doesn't exist...

All are parasitized, that's the normality. The variety, the deviant subspecies, has hardly appeared. The variation, the speciation, will take place only gradually. The time of the Tempists(those who adapt to the chronophysiology of HIV) has not yet come. The numerical threshold has not yet been reached. But it is coming...

4/7: we hope it will not go further

From a doctor, about the 4/7, I heard, once: 'we hope it will not go further'. There, I remained on the ass. In what way? Where does she get this from? Where does she get it from that we hope it will not go any further. Of course it does! Between Iccarre, ANRS-4D and Quatuor, you have about 1000 patients in 4/7, under the title of the trial, in success. And about 1000 other title of what Morlat allows it, since 1000 days, already! And that it begins to do well!

You can imagine that among the number, there will be some who will have skipped a few doses, inadvertently, while remaining undetectable. In ANRS-4D, there are three assholes who have been found out, but there are those who have been missed. They know it. Then there are others... who think.

So they'll ask their doctor (septistic, not yet fired): why don 't we go to 3/7. Oh, don't think about it, my good girl, 4/7 is already enough! Really??? And the failure rate at 3/7, how much is it? How much is it!?

We have never seen anyone fail Triumeq® 3/7, nor Triumeq® 2/7. Same with Eviplera® 3/7. Show us failures! Yes, show us! The demand for proof is on the other side. All these people who talk about it, they have nothing (real) to show. When I spoke above about condom for small cock, it is well of that: if you have finery, show them! Let's see what happens! If you have artillery for real, then shoot it! Or else, shut up!

Especially since how do you want Merck to increase sales of its MK-8591, the EFdA, the one whose half-life allows a weekly intake? They're going to say you take What's-His-Name® on Sunday and Truvada® every day? That's silly... The only way Merck can get back in the game is with MK-8591, and its only commercial advantage is that it's weekly. It's not with the little Doravirine that they're going to get back on track. Now we're going to laugh! Anyway... Apparently Merck has sensed the trap and intends to foil it with 2 tricks that we will understand by reading this article and this presentation of Pr Molina: we are going to have fun! Because we too know how to turn the situation to our advantage.

And then, the ostracism will change sides. Everyone will be worming their way in, bending over the toilet bowl, naming the beast after Prof. R***, Prof. M***, Prof. P***, and... Flush

In the news

- The tiger mosquito almost eliminated by a new method of control (source: Futura)
Before the middle of the 20th century, Darlington stated: 'It is not far from heredity to infection'. A vast subject! The spermatozoon brings nothing but its chromosomes. 'The spermatozoon is the bandit in its pure state, said Cioran. From there to see in the male only a parasite... Or in the virus, only a male.
Think of it this way: the virus as a spermatozoon, fertilizing the CD4, giving birth only to ... males, while practicing parthenogenesis at all costs.

- The cycle creates a selection pressure: it is not in the press... I am the one who wrote this... We will come back to this

- Islatravir : presentation of Pr Molina: 3 doses of MK-8591 (0.25 mg, 0.75 mg, or 2.25 mg) are equally effective: let's see what Merck will choose... Hi, Hi, Hi... Not necessarily the strongest... And even, we are talking about 0.2 or 2 mg ! See how, with my discussion on DTG-25 mg, I am probably far from the mark!

The French genius: QUATUOR is TOP!

Moment of glory for... Dr Roland Landman, who presents results from Quatuor. One can read with amusement the comment of Margolis, once a researcher who found nothing, now a ViiV employee (Director of HIV Drug Development at ViiV, the article doesn't say so...). The buzz is here:

QUARTET: IT WORKS!!! .

Well... I'm very happy, and so are you. There is nothing to say: it is Nickel from Nickel. Really, it's CHAMPAGNE!

I don't know what to say in this case: Bravo! Congratulations! Legion of honor! Leibo, you are the most beautiful...

Oh yes... A last word for the road: take a deworming and get rid of the secret doctors! Quickly!! It's urgent!!!



overmedication is an opportunity if you know how to take advantage of it!

127

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



DTG-25 mg episode 4

By Charles-Edouard!

Here's a Patrick who would have done better to understand intermittency than to play the fool.
This is what the omerta on the intermittence gives: the moral responsibility is in the opposite camp. Sensitive to false testimony, and with a mind obviously clouded by overmedication, this is one person who has been totally closed to our arguments. ARVs freeze the situation; in the absence of active replication, the lymphocytes return to a more usual equilibrium. When they thaw out, they return to their former equilibrium in a few months. Therapeutic vacancy in LOTTI or SALTO conditions is favorable. For those who have already passed through an AIDS stage, such as our Patrick, it is the announced disaster (some of them manage to control their disease for a fairly long period of time: the PTC).

The septists have the double punishment: the infamous responsibility of overmedication, and, boomerang effect, the aforementioned Patrick will finally understand that intermittence (ICCARRE/OMNIBVS) is the uninterrupted maintenance ofthe viremic suppression. Let's hear it...

DTG-25 mg: necessary dosage vs usual dosage

The two tables, made public by ViiV(see episode 3), are rich in information: there are no yellow, orange or red primary mutations under DTG, but there are red ones under RAL or EVG: under RAL or DTG, you almost inevitably need 2 other molecules to block the possible appearance of mutations that would make RAL or EVG inoperative. Under the old INIs, these red boxes require IRT, including in group 1 (naive or successful patients), or failing that, in maintenance, a BI in a well-synergistic couple. Moreover, EVG is ONLY available in IRT, and the admissible reason is this bright red table; without even mentioning the second table (successive mutations).

On the other hand, it is not surprising that MONO-DTG works! It is right there under your nose! And obviously, if you have been through RAL or EVG you are at risk: secondary mutations may have appeared surreptitiously, and you may be in the case of table 2, and there a third molecule (or a double dose of DTG) are useful or even necessary. No one will ever tell you that, Merck because RAL is on its last legs, Gilead because they hope to convert EVG to BTG (Biktarvy) and ViiV because Mono-DTG takes 25% of their profit. Not even the FDA, because their specification is flawed.

I made a small synthetic diagram, inspired by the poster of Seki (ViiV, CROI-2010). Here, it is very clear!

Phase 2 ??? What phase 2? Nothing to beat...

You, you thought blithely that the phase 2 trial is used to determine the minimum dose required for maximum effectivenessYou try several doses and you take the one that has the best result, at the lowest dosage. For Evafirenz, the trial is clear: 200 mg should have been chosen, and many suicides would have been avoided and many more patients would have had access to treatment. The Phase 2 trial serves a purpose, otherwise why do it? Well no... We do it and we don't care... The proof by Fujiwara(ViiV powerpoint, here):
Maximum tolerated dose is not minimum effective dose!... But the most shocking is the 'A priori...' which is defined as follows:
1. Starting from data prior to the experiment.
2. At first sight, before any experiment.
If you choose the dose BEFORE the experiment, you have made a decision, on paper, without any intention of taking the phase 2 trial into account.

The trial is mandatory, but it is not mandatory to take it into account!!!

So what do you do if you can't tolerate the maximum tolerated dose (like 10-15% of patients, at 3 years)?(see ANRS study)? Do you switch? And for what? And why? Whether you tolerate it more or less well, or even very well, why stuff yourself at 30 Euros per day?

So you have those who laugh at the effectiveness of DTG, some who regret the dropout rate, higher than in the advertisement. But, not one to go and look at the phase 2 trial. What is the point of trusting doctors who don't read the trials. Did they get their diploma in a Bonux package? And, when did they get this old-fashioned sesame?

Scam? But where is the scam?

Indeed, someone takes a zirconia and sells it to you as a diamond, there is deception; if a 300 mg pill has only 100 mg (or plaster), there is deception. But how does the manufacturer benefit from overdosing? Try to think about it...

Let's take an example closer than rosuvastatin:
For HIV, Lamivudine is in daily dosage at 300 mg/d. at a price of 69.42 ���� (Reimbursement rate: 100%) by Mylan for 60 tablets of 150 mg, scored (source)

For HBV, the same Lamivudine is in a dosage of 100 mg/d. Price : 88,43 € Reimbursement rate : 65% for 30 tablets(source)

For 69 Euros, reimbursed, you have 60 pills of 150 mg; for 88 Euros, you have only 30 pills (100 mg): it is twice as expensive (taking into account the reimbursement), for 3 times less!

The average Frenchman doesn't see the trick, but the average American, without social security coverage, quickly understands that buying Mylan 300 mg (in fact 150mg x 2), cutting it in 2 (or in 2/3) will save him $50 per month. $600 a year for the little lamivudine of my two....

When the price is crushed, i.e. not in proportion to the dose, then the retired, the poor, the parents of infected children, all will jump on the bargain; and it is as much loss of profit for the manufacturer...

A little thought before the next step

To get a head start on what's next, try to imagine for yourself what a base dosage of 10 mg would have meant for the healthcare system, for profits, and also for yourself, as part of maintenance.

Some people think that by doing 1/2, they are doing intermittence, the only proven way to dynamic remission: this is incorrect: they are only correcting the dose, wisely, as we will see.

Others say that if they do 3/7 or 2/7, they are lucky to be the 'happy few', the privileged ones... But where do you get that from? Do you know the failure rate for 3/7 maintenance under Triumeq ® ? Have you ever seen someone fail at 3/7 (or even 2/7)? In MONO-DTG, if we are not careful, there are failures, but not in those who minimize the risk (good compliance, no Achilles' heel and/or early initiation). So there, Happy, Yes... Few, No!...

When injectables arrive, at an exorbitant price, are you really going to inject the whole dose? every month? For life???

If you think that overdosing is a malpractice, look to your doctor, who, in the chain, is the last but one before you. The doctor has every right to advise you to take half a Tivicay®. It's his job, the useless privilege of not using it

Over-medication is an opportunity, as long as you realize it and take advantage of it

OMNIBVS

I'm in OMNIBVS all the way and, despite a unheard of adversityI've just won a decisive move. A great thing that changes the game, so morale is up!

Especially since the first batch of 1/15 is on its way! This is also really important and as soon as I'm done with DTG-25 mg, I'll give you my thoughts about the transition from 2/7 (Triumeq® or Eviplera®/Odyfsey®) to 1/7, then 1/15. Yours truly continues his successful descent, currently at 1/10, with the NFC (Nouvelle Formule de Charles-Edouard). The first one is for those who will have provided an email address, which can be done simply by leaving a message here(email addresses are not published, of course).

Judiciarization

- We had announced here that ViiV filed a complaint against Gilead for plagiarism (Bictegravir). We will soon resume the investigation. Indeed, new, imperceptible movements give us the keys to a secret YALTA, which redefines, in all discretion, the new power relations in the medical-pharmaceutical underworld. To be continued...

In the news

- Massive attack on Nevirapine. The disappearance of Videx® from the shelves has taken the orthodox iccarrians by surprise. They were almost the last users in France. Eventually, Videx® will have to be replaced... This explains the urgency to launch OMNIBVS without delay. I don't understand why they don't see what's coming, confident as they are in their temporary solution: they are wrong. By the way, this is exactly why I didn't want to get on that train, even though it was well underway, and why no clinician wants to take up the torch from that angle. It's a shame, but hey... We'll find a solution... I mean... We'll... Other than me, I don't see a lot of people...

I have more confidence in Nevirapine, which will always be marketed in India or China... But in France? Its days are counted if we are not careful. I will comment further, get ahead: Nevirapine Explainer May 2018 (US Congress), the DTL strategy.

Good Weekend, good stuffing and not too many meds ... Right?

126

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



DTG-25 mg episode 3

By Charles-Edouard!

In margin of the Lambert Affair (out of our subject, here), a letter of Dr S. PALIARD-FRANCO:

Oh, come on!!! Science and Faith are not in harmony. It is a misplaced trust to place it in those who privilege conviction over proof. Joyeux is a religious activist, almost homophobic... Here is a doctor, writing, in her capacity, to another, Minister of Health, who affirms, right in the eyes (as Dr. Cahuzac would say): by his will, he could have contracted a fatal infection. A deficiency in cellular immunity on demand!!! The proof of his will would be that his immunity, autonomous, insubordinate, works... And, in addition, one could even choose the infectious agent for oneself... One can commit suicide at the first pneumococcus passing by. It is the other side of the same joke that would like the force of conviction to heal, miraculously, a Lourdes in reverse, so to speak.

Many people place their trust in soul supplements (homeopathy, prayer, yoga, overdosing, overprescription...) that viruses, bacteria and macrophages have no use for. We must denounce it. No! criticizing an idea for being false is not a discrimination. Mocking an 'invert' (cf Joyeux), is! To affirm that the Faith of some does not cause harm to others is inaccurate. Misplaced conviction rots everything around it.

Let's go back to our sheep, with our minds cleared of this parasitic nonsense...

DTG-25 mg episode 3: DTG-50 mg, criminal chemical incarceration

This is also a scam of a somewhat original kind. As in prestidigitation, the trick is to divert attention from what is actually happening. The context dazzles us, collectively, and we get distracted, including by the question of Mono or Bi therapy, while the trick, the deception, is right there in front of us.

Their novel is an affabulation for the enlightened. They have committed their crime, before our astonished eyes, and have even signed it: the culprits have named themselves as if to better conceal their cheating.

We had already drawn up the picture:
- the original pharmaceutical sin: the slant and the S
- the escalation test is mandatory but they don't care
- EFV 600 mg an unfortunate precedent
- the trauma of multi-dose rosuvastatin
- DTG and the famous specifications

Our investigation continues...

The curse of efficiency lost but not quite

During pre-clinical development, they will realize something that will satisfy them while posing an unexpected problem. DTG is remarkably well designed... In the laboratory, after many attempts, one always ends up selecting mutants; one cannot think of biology without Evolution. The mutant loses fitness, of course, but gains resistance. It gains more or less resistance. If it gains a little, it remains susceptible to about the same dose; if it gains a lot, the molecule loses its effect, almost completely: the dose must be multiplied to overcome it; this multiplier coefficient, FC for Fold Change, is the indicator of this loss of effectiveness. It is quite well known: the mutation at position 184 confers a resistance to Lamivudine with a moderate FC (ca 3.5): it remains usable. Q148K gives a FC of 83 against RAL and 1700 against EVG: here one should not dream anymore, one would have to multiply the dose to stratospheric levels to overcome it.

Under DTG, and in patients naive to INIs, it is almost impossible to develop mutants with moderate or high FC. Seki explains here:
All single mutants [...] do not alter [DTG] activity by more than a factor of 5.
Fujiwara completes here, I quote:

On the other hand, if you already have a mutant, typically acquired under RAL or EVG, acquired by you (a failure for example), or by whoever gave it to you, this mutant can mutate again and have a moderately high FC, high but not prohibitive: FC between 10 and 20. That's a lot and not too much at the same time. It would have been better if this FC had been a bit lower, but 20 is playable! Hooray! We will be able to bring a solution to the patients of group 2, those who are up to their necks in shit. And at the cost of a higher dose. The FDA will give you anaccelerated MA, which will allow you to exploit the patent for another 2-3 years .

So for group 1, you're going to need a dose for HR < 5, and for group 2, you're going to need a dose for HR between 25 and 50.

A dose for group 1 and a dose for group 2: and these are not conspiracy theories: there is indeed a dose for group 1 patients and another for group 2 patients: this is written in the instructions in the box!

One dosage for some (the vast majority), and one dosage for a few others, perfectly identifiable.

The problem jumps out at you: the requirement is a ratio of 1 to 10, but the suggested dosage is in a ratio of 1 to 2. Can you see the trick? The CF is low for group 1 and ten times higher for group 2, with the icing on the cake that you can't switch from group 1 to group 2. 2 needs, 2 dosages, but the ratio of needs and the ratios of supply differ by a factor of 10!

And the whole aberration comes from there! If your cab chooses a slightly longer route, it passes... If it goes around the ring road 10 times, it's a real swindle. Well, it's the same! At 50 mg, you (from group 1) are swollen by a factor of 10!

The curse of lost-but-not-quite-effectiveness could have been a problem for ViiV, but they're going to pass the buck, and the curse is now on you. We'll see next time how ViiV will succeed in his trick, no one knows...

Towards the obligation of treatment / Judiciarization

David Hynd must attend daily appointments if his HIV levels exceed a certain threshold. Read here. This is the first time that British Columbia has use the courts to force someone to take a treatment against HIV. Let's bet it's not the last... What's up? We didn't tell you about it?

In the news

- DOVATO (DTG/3TC Combo) is announced! What??? The Gilead-o-latre media is not telling you about it ???? Of course, there will always be some idiots who will entertain doubts and lead the poor patient into a daily and deleterious TRI. And others to believe that it will be cheaper. 27,540/year Still!. It's too expensive for Lamivudine ($6600/year for a generic sold for $30/year to NGOs and $300 in India) and 50mg of DTG, which is far too overdosed! Our discussion on DTG-25 mg is very timely!

- especially since Mono-DTG just won a landslide victory: Non-inferiority of simplified dolutegravir monotherapy [...] randomized, controlled, multi-site, open-label, non-inferiority trial. The ViiV stipendiaries didn't tell you about that either! We did!!! and we will come back to it in detail! (read also: Predictors of virological failure in HIV-1-infected patients switching to dolutegravir maintenance monotherapy)

- Atripla® in 1/2 dose works as well as in daily dose: We already knew that! We have the confirmation here: Randomized clinical trial of the efficacy of every other day fixed-dose efavirenz/tenofovir/emtricitabine versus continuous therapy. When is regulatory listing expected? Morlat, are you there? Morlat, do you hear?

- Hurray!!! Finally a study that shows that the Eclipse is manipulable: We demonstrate a reduction of the reservoir by measuring what, only, we care about: the Eclipse. The new Gilead's 'shock and kill' clears deadly virus in monkeys. As usual, the natural Eclipse is, in median, 21 days.

The French genius

What is this cool music you are listening to right now? Oh, in its reference version by the lovely Scott Ross, it's a bit abrupt; KEMPFF makes it subtle, audible, invites us to to bird recallby J.Ph. Rameau, otherwise a bit old-fashioned. If you liked KEMPFF, you might like his Bach Sicilienne BWV1031

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overmedication is an opportunity if you know how to use it!