136

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



Dodecadism

By Charles-Edouard!

We are now far from all this:

Sometimes you have to wait to see them disappear too... Well... All this is far from me. Phew!...

Dodeca means... 12

Of course there are not 12 molecules! The idea comes from the analogy 'bomb (atomic) - silence'. I stood in front of the door of the 1/30 temple. At 1 in 30, you are the king of oil. So, when the virus goes up (a little) to 1/27, you're left with a dumb one. So close, it's infuriating!

For a while I hoped that DTG would be the decisive tool to get over this barrier. I explored, and, well, if it is, it's not obvious. But with Islatravir, it's bound to be different.

In the OMNIBVS approach, we will first prove the 2/7 on a large base, even if it means inflating the combo a bit, then, once the 2/7 (or even 1/7) is proven again (if the FASEB-2 proof is not enough for you) we can consider reducing the combo.

But is it really necessary? Someone was wondering about replacing his RPV in Eviplera® in 2/7, because of a minor mutation to RPV in his genotype. Why replace? Just add. It is true that RPV decreases a little the concentration of DTG, but not as much as NVP does. It is not clear whether adding a molecule is necessary, but it is sufficient and with ridiculously marginal toxicity.

Let's take examples of possible combos at 2/7: Juluca (DTG/RPV) + Truvada (TDF/F-3TC), or DTG/ATV + Truvada or NVP/DDI/TDF/F-3TC, or Biktarvy + RPV: these are perfectly bearable quadritherapies, at these homeopathic doses!

Why bother trying to optimize towards less, knowing that when we will be at OMNIBVS 2/7 (or even 1/7), the panel of available molecules will have changed? At this rate, we'll never get there.

You have to live with the times:

Some molecules appear, others disappear. Videx has disappeared from the shelves: it was BMS that killed it. We can live on the stock for a while, but the orthodox ICCARRIANS are already in a dead end: it is only a matter of time. Now, in the magic combo (patented) NVP and DDI form a couple: if you can't use Videx anymore, you have to replace it. Yes, but with what, knowing that NVP is not compatible with DTG (nor ATV, to a lesser extent). ABC? Yes, maybe, but it's not great in this context.

A hundred patients are going to the wall. Obsolescence is part of the pharmaceutical hold-up. Especially since to find a fresh doctor who prescribes NVP, you'll have to look!

As far as DDI is concerned, we won't cry too long, but you'll have to explain to me how dynamic healing is done without NVP! Which is probably the most efficient for our purposes (go figure...). The Great Turtle combo(if you don't know it, google it!) is OUT. Gold, OMNIBVS has to live...

When there are so many drugs, why bother?

The MOAB bypasses all constraints

Well... The use of the atomic bomb is a dirty business. Under the supervision of Donald Rumsfeld (you know... the mythical boss of... Gilead), the Americans have developed the Massive Ordnance Air Blast Bomb (MOAB): it's far from Hiroshima, but it's 'conventional' (sic). MOAB, it means rather Mother Of All Bombs (the mother of all bombs). Well, we put everything we have at hand and BOUM!

The dodeca is the same: we put everything we have at hand. And it's quite easy: let's say we start with Truvada® + Efavirenz (or NVP) and we make it 3/7 or better, as usual. The result is a large stock... We whine a little (or a lot) and we easily get a switch to Juluca, and the extra CVs that go with it... Well, here it is: you have the ingredients for your own recipe. This is your recipeYou have the ingredients for your personal recipe, not mine, and no one is there to tell you'this is it and not something else'.

Your Truvada® supply will be running low... Slowly! Because at 2/7 (or even 1/7) it will take forever! You will find a solution. That's what the internet is for, right? The PrePers are doing it well, so you can do it too. And then, after that, comes Islatravir, Doravirine, and so on and so forth. When you walk around at night with a flashlight, what's in front of you lights up and what's behind you goes out. It's as simple as that.

Dodeca, it still means that you have to pull yourself up by your bootstraps a bit: have several doctors (if needed), make your CVs. You can be in the patent orthodoxy and still be free. Being free does not mean doing everything and anything... And I call it Dodeca®. It's a great tool for exploring and then exploiting the Eclipse. And we try not to be too stupid: we avoid incompatibilities and hypersensitivities (in 1/7, we lose the mythridatization, e.g. ABC), Isentress ® which does not work.

My doctor knows how to do the 1/15, in Dodeca! If... If...

It's not the genius of the mountain pastures for all that! But since I came out, I might as well go all out. I start my coming-out with an introduction. I tell him about the eclipse and ask him how long it will last. Surprised, he tells me: a fortnight. Not so stupid, eh? There, you feel the surrender... And then the 1/7 that would make any 7/7 bigot jump up and down passes like a letter in the post. The next time you come with your suitcase, and you show him all the stock you have. You say nothing... The guy understands right away that you're the one in charge. If he doesn't do what you want, you go somewhere else, that's clear!

He gave me two prescriptions that knocked me on my ass:
- a CV prescription every month (valid for 1 year)
- a prescription with ALL the molecules that an honest girl should have (renewable eleven times, in 7/7, moreover)

He handed them to me, as if to say ' I'm a smart guy, I'm a smart guy'. Here's your paper, you're on your own.

Well, that's it! It is not more complicated than that!

I only take three molecules from the pharmacy, under the very real pretext of sufficient stock, where I only go once a quarter. And I go to the lab according to MY schedule.

Phew... So it was so simple.

This is how I do NFC3 (Charles-Edouard's New Formula), and don't ask me for more because I'm not the one who solves your problem: it's up to you to get off your ass.

My 1/15

Well... the first beacon went well. Nothing to say... Taken today, and appointment in 2 weeks...

OMNIBVS

The presentation that is now circulating among race clinicians is available here. It will be on youtube soon.

In the news

- Here is a video that will instruct the most novices: for us, here, it is far behind us, but let's admit that it will increase our potential audience, which is rather good... That's the whole point of Quatuor, to allow the regulatory registration of a procedure already authorized elsewhere. The problem is that this is its only interest: It's still a little piss-poor.

- Artificial intelligence invites itself to the personalization of treatment. We would have preferred intelligence at all. This is the stupidest, dumbest article of 2019! I don't understand how anyone can be so stupid... This is what happens when you put a 'black box' software in the hands of doctors. Of course, the usual parrots blindly echo it... It is so stupid... Especially since their stupidity is displayed in their diagrams: Science without knowledge is but the ruin of the soul... And you, will you be able to find by yourself what's wrong?

overmedication is a chance if you know how to take advantage of it!

135

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



New Horizons: over-14, over-30

By Charles-Edouard!

Pharmacokinetics, which has nothing to do with the Eclipse, has a thick skin!

What about us??? At 1/14, we don't ask ourselves the question! That's when we see! The Eclipse is the elephant in the room! We finally see it and it's Eureka!

First 1/14, first 1/30

I anticipated, in the previous post that 'on 14' was quite necessarily the new Frontier.

My first 1/14 from 2015 is in this post. 4 years already!... I was stuck before 1/30, and was hoping in DTG, which, as it turns out, doesn't necessarily offer what is missing to close the gap. As far as I know, I was the only one to have explored the Eclipse from top to bottom, from 1/7 to 1/27 (closing). Honestly, I was very satisfied!

There is a point where it comes up! And the further you go, the closer that moment gets. This leads to the following paradox: at the beginning you explore 1/8, 1/9, 1/10 by steps of 1, and you get bored!

Then you advance by steps of 2, to simplify your life, and, probably a mistake, you advance by steps of 3, where you are in fact close to the cliff. In all good logic, you should do the opposite. Move forward in big steps at the beginning, then more cautiously: 4/7, 2/7, 2/9, 2/11, 2/13, 2/14. But we will see that there is still more to do, in my opinion.

To each station its problem, its optimization, its combo

At each stop, which we call station, a new landscape is in front of you. No one would ever think of doing the Quadri-Leibo in 7/7! Everyone is wrong here... And a clinician says: 'don't count on me to prescribe Videx'.

I hear that... But that's not the question... The question is to prescribe Videx in 1/7, which is obviously a different context. Tomorrow someone would prove to me that AZT would allow me to make the link that I lack to go from 1/24 to 1/30, I would go without hesitation!!!

The 'on 14' has always existed

It is as old as ARVs! It's even very old! Well... You still don't see ... It's even the very first try... Still not? This is the 1 week ON 1 week OFF, which in our now accepted notation of x consecutive days is written 7/14... Here it is!...

The interesting thing about the 7/14 is that we dissociate the Eclipse from the choice of the combo: If you fail at 1/10, you don't know if it's because of the 1 or the 10. If you succeed at 7/14, you already have a good idea about the Eclipse, which you see, it's there in front of you. And if it doesn't do it, it won't do it either at 1/7.

Hence this proposal: 7/14; 6/14; 5/14; 4/14; 3/14; 2/14. That wouldn't be a bad New Exploratory Schedule. And with the long-acting molecules (NVP, DTG-and-copies, Islatravir), it's encouraging. Finally, there is no particular benefit in redoing ICCARRE, identically. Firstly, because it has already been done, so we know. But ICCARRE is done with molecules that are in disarray (Videx), in the hot seat (NVP), or flat (TDF/F-3TC).

With the new molecules, we can consider throwing the piggy bank further. Because at 2/14, or even 1/14, the injectable is no longer of any interest. And Merck (Islatravir) has to fight on 2 antagonistic fronts: Injectables (ViiV), and zigoto-4/7 in generics, which, for the time being, will appear to be of unparalleled boringness. And Merck is going to hide the main characteristic of Islatravir, because it must piss them off!

Afterwards, when we know how to do the 1/14 with Islatravir, we will be able to look back and see that there wasn't really that much difference between NVP and Islatravir, in terms of intracellular persistence. How stupid we are, we could have realized it before!!! Well... Yes...

Liberation Day

Here is the table of release days, according to the intermittence profile followed.

Rhythm	Liberation on...	Comments
4/7	July 28th	It's boring
3/7	June 6th
2/7	April 15th	it gets interesting
1/7	February 21st
1/14	January 26th	I'm here: cool
1/21	January 17th
1/30	Jan 12	With Islatravir? injectables = no thanks

My 1/14 and new flexibility

I missed the blood test, having preferred to coocoon some time after a difficult trip. I have a new flexibility: In x/7, I take the blood test on my birthday and I take the meds directly after the blood test.

In 1/14 (or even better), I plan to do it on day 13 or 14, so I have the possibility of a catch-up day. As the French labs do Shabbat (an outdated tradition...), it limits a bit, but well, it's only a few times a year.

In the news

Trulight: it's nothing, just noise... Who wants to take Truvada® 7/7 today? Barely 20% of patients have a reservoir < 800 cp DNA/million PBMC, and, taking into account the inclusion bias (de facto average CD4 = 800, endless inclusion), the potential target population is barely 10%, for a 10% failure rate... So, yes, it works for some, and good for them! And to the 90% who didn't fail, we ask the question: what do you do now? This test does not concern us. Now you know, and that's a good thing!

Mediator: (Here, an article from Le Monde) the whole trick of Servier is to have diverted the attention by pretending that their molecule is not of the class of FenFen (fenfluramines): We will see Merck doing the same with Islatravir: they will have to make up: we will soon see why...

The French genius of cold (brrrrr)

Mythical version by the unforgettable Klaus Nomi, gone too soon... The versions with bass are more accessible and just as chilling. See also here. Recently, Abdelazor's rondeau (Purcell again) has been brilliantly performed by X Varnus and B. J. Samodai. A more classical version here.

Feel free to comment, like, share and use

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

134

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



The 1/14 is already healing a little...

By Charles-Edouard!

You'll have to get used to it:

Having followed the story for a long time and having fought with our friend for a long time, this is an honest testimony. There are now 2 of us, since I have just switched to 1/14, with an inflated combo. Our friend had a very small CV before treatment (3000). I'm a fan of the 'big bomb, long silence'. If others manage to do it with just a small grenade (DTG/3TC), well, all the better!

As for me, after my failure of DTG 150 mg 1/7, it is understandable that I don't do DTG/3TC in 1/14! Everyone does according to where they are and how they get there.

1/14, release day and social security contribution

I am for solidarity, but against abuse. Until recently, the basic young homo paid, on his workUntil recently, the basic young homo paid a family allowance contribution, which you'd have to be really twisted to think that he'd ever benefit from it. Everyone is exposed to unemployment or health risks: the contribution gives rights. No! I am not exposed to the risk of having many children! I find it disgusting to contribute through work. Through taxation, that's another thing. Very recently, the thing has been put back in order, which proves that my aversion to an iniquitous system was justified.

For health, likewise: there are young people who enter active life by being, from the start, net debtors of the system. A young gay man is 200 times more exposed to HIV than another! Fortunately, there is PreP (free) to set the record straight! A young Chinese gay man is overexposed to the risk, but his treatment, in the second largest economy in the world, is $60 a year! Some people like being a net contributor. Oh, I know the crybabies (profiteers) feel differently! Good for them: young gays vote with their feet and go live in Canada, Switzerland, etc... Where they are not subject to financial discrimination. France attracts poorly qualified people and turns away its graduates. And if you think that young German engineers are rushing to our borders for the privilege of financing the CAF, you are wrong!

To be a net contributor is a credit to those who find it abusive to unduly exploit a natural inclination. We will see, with Islatravir, that its invention did not cost Merck a penny, which is going to make billions on your back: that is the medical-pharmaceutical underworld. The CPAM will benefit from a windfall of hundreds of millions, thanks to the 4/7. Do you think for a moment that they will say thank you? Or that they will have contributed at all to its advent? No! Stipended 'assocs' are slowing down ! Have you seen them positively echoing Quatuor? Not even! All this little world is living off youNot even! a little less each year and good luck!

The 1/14 is not a beauty contest

For the 1/14, release day is January 26! 1 year of your treatments serve us 14 years. So let the 7/7, in maintenance, go to the end of their frightening logic and pay for the part of the drugs that do not make them more than a placebo or a food supplement!

I understand that trying 3/7, 2/7, etc., there are some who fail and must resume the same treatment at a more sustained pace. Getting to a dynamic remission may not be for everyone right away, and it will be quite technical, a technicality that your doctor(of my two) does not master. So what?! So what?! The one who arrives at the 1/14 marker, she doesn't care!!!. We have the right to explore and exploit an Eclipse whose existence is not in doubt!

It is not the race to the shallot. Anyway, the person who is at X/7 will necessarily ask himself one day the question of (X-1)/7. It's only a matter of time! And, with the arrival of Islatravir, the first molecule duly stamped: 10d. or more, things will move!!!

I'm pushing for a 3/7 trial, the only quick way to prove the robustness of 4/7; I'm pushing, but not more than that... The advent of 3/7 is inevitable (with Odyfsey, for example)

And our friend here has succeeded in 1/14 with DTG/3TC, without bloating a bit, but again, it is only a matter of time before he tries 6/21, 5/21, 4/21, etc. When Islatravir becomes available, will he substitute DTG for Islatravir (moderate genetic barrier)? No! he will add it, and there it is in TRI (or even Quadri, because they will be smart and forcefully combine it with Doravirine)

And, of course, the collaborator of service to persifler:

And to the question: which doctor? She never answers: and for good reason! Even Leibo is useless to us on 1/14, so useless at 1/14 or useless at all, it's the same

Obligation of treatment / Judiciarization

The USA is a theocracy, in case you didn't realize it... Here, in France, we are in the middle of a vaccination frenzy: But [the HAS] also raises the fact that 'HPV vaccination limited to girls and MSM raises questions of ethics, equal access to vaccination and stigmatization linked to sexual orientation and non-respect of privacy'. source: LeMonde

Well no!!! Vaccinating young gay men against HBV, to which they are more exposed, is a rather good idea, despite the proven risk of multiple sclerosis. The increased risk tilts the balance in favor of this vaccination, which I did myself, as such. Never Oh never, have I felt discriminated against for doing it and others not!!! This is ridiculous: we cry discrimination for everything and anythingThe side effects of this vaccination will not be detectable by the health care system, and we are heading towards a new health scandal.

We remind them, and the ActUpians too, thatthere is a jurisprudence, called Nuremberg jurisprudence (which is not nothing), which says that one cannot inflict a medical act for the benefit of others: It is not that eugenics does not work, it is that it is contrary to human dignityIt is not that eugenics doesn't work, it is that it is not: no, the massive HPV vaccination will have only a marginal effect. In Australia, which is an island, there is a very small effect (and none on cancers), and they don't count the side effects, because they can't make the correlation. That's right, you can't make the correlation... So what? This does not invalidate the suspicion of cause and effect. We are in the middle of a ridiculous situation and it was urgent to fire the ex-ActUp!

Have a good weekend, get drunk and don't take too many pills... Right?

133

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



The anti-Quatuor, episode 1

By Charles-Edouard!

No! Simon Collins is not my friend nor my cup of tea...
I know neither the person nor his intellectual path, so I won't criticize too much. The little I have read of him has left me indifferent, at most. He is one of the pro-treatment, stipendiary activists, who, by dint of their efforts, acquire a semblance of knowledge, which one would be wrong to take for insight. Seeing him dumbfounded, like so many others, in front of the START trial without being able to dismantle its traps was enough to make me distrust him. On the other hand, it would be useful to explain the 4/7 to him.

Even a very well-informed scientist can be taken in by the apparent solidity of a clinical trial (e.g. Dr Dupagne and Levothyrox): the devil is in the details and to sniff out the methodological error is not within the reach of anyone, including the best (de)trained by the University.

With all due respect, I deny to my acquaintances, including those with a solid scientific background, the capacity to be able, on simple examination, without debate, to flush out the traps of interpretation. Being an activist does not seem to require more qualifications than being an apprentice hairdresser or an enarque.

The judgement may seem harsh, but I apply it to myself, for having let myself be deceived for a long time, to which stipendiary activists will have valiantly contributed. So... Too little for me. Thanks anyway!

Quartet from scientific success to media flop

Well... The communication around ANRS-4D was an instrumental disaster: nobody really paid attention, the presentation took place on the other side of the world, and de Truchis had to admit, on his return, that the ANRS had made mistakes in its reading of the project. This error was admitted in front of the 'Tout-Paris-qui-compte', but was hidden in the English publications: how can the average evangelical-lutheran understand it?

Right from the start, the way Truchis et al. go about their work is marked by this infamy, for they have to argue, without denying what they have not been able to say, even before having taken the time to analyze the failures. Analysis, which, for us, explorers of pharmaceutical remission, still counts for something!

Poor Dr. Roland Landman stated that:
It seems that the Durban fiasco (ANRS-4D) was not enough for them!

Quartet... An attempt to convince... The Americans!

The practice of 4/7 spreads throughout France, good or bad... Pr Jean-François Delfraissy, infectiologist (at minute 3:12 of the original source, alternatively the true verbatim here) on the results that we are going to produce
Obviously, spending French taxpayers' money for the sole benefit, quite hypothetical, of convincing ignoramuses, and holding back the beneficial advent of a French invention for the French patient, is perplexing... The trap closes on poor Roland, who obviously does not have much to lose: the treatment is still ungrateful for his valiant scientists who succeeded, after all, in validating a procedure that was already authorized! We will always be surprised by the clever opportunism of Morlat who cut the ground from under the ANRS's feet, by recommending 4/7 even before Quatuor!

Quatuor in the international 'press

Here is what I could find... If you find others, don't hesitate to report it:

Website	link	Comments
IAS-2019	link	the original source
TheBodyPro	link	You can't be more succinct
i-base	link	ignorance in the service of Big-Pharma
aidsmap	link	chip/paste
MedPageToday	link	The voice of his master (ViiV, here)
eatg	link	(broken?) 404 error
corevih-bretagne	link	Arvieux: Snipe on the go and provincial oxymoron

From reading the article here, it sounds like there was a press conference specific to Quartet? I don't know if there was, but then, the 'press' didn't rush to the progress made on the road to remission. They need something more spectacular! Blood, blood!!!

And at ICCARRE? Not a word...

Snipe on the go and provincial oxymoron

Let's have a little one for the road: the oxymoronic Arvieux doesn't hesitate to write: and, a little further on:
In other words, in the same piece to say that we have a tradition, ten years old, established, with proven effectiveness, but besides this Quartet(futile, let's not doubt it), that it (you) will still need results in the longer term... When it comes to napalizing the whole world with dolutegravir, we don't take so many precautions!

Well, we'll see the other fools another time... Until then, try to imagine what effect a negative result of Quatuor would have had (on you, in particular, and on medicine, in general). Assume that the 4/7 would have been, say, 15% lower... Think about that... Would that have changed our perspective? Hi, hi, hi... Think about it!

Feel free to comment, like, share and use

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

132

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



Help yourself: ARVs will help you

By Charles-Edouard!

The blog is assailed by SPAM, so: on a recent article, the messages are published immediately. On an old article, they are moderated...

Intermittency is unstoppable

When you're at 4/7, it's normal for 3/7 to tickle you. Each time, you are there and it works. And as it works, you are there; so why not go further? It's Darwinian and recursive: at each increment you, and your virus, are in a new environment. There is, strictly speaking, no intention. Some people stop, at the judgement, the pre-judgement shall we say, at X/7. But this is only temporary and it is only a matter of time before they resume their journey, each time more astonished by their extraordinary success: they believe it to be exceptional: it is not! Find me even one failure with Triumeq® in 2/7 or Eviplera® in 3/7!

The intention, or the goal, shall we say, is most often the fear of side effects. Once at 1/7, we can say, for sure, objective achieved! However, there is nothing objective about this: reducing an overdose by a factor of 15-25 (e.g. DTG) by a factor of 7 is not an objective success.

Toxicity is not my initial motivation

My entry into intermittence had nothing to do with toxicity, which, like many, I had not identified as such, and which had already done its work of undermining, with consequences and after-effects that would be discovered and that the simple change to 6/7 would reveal. I am familiar with this state of mind of the patient who does not see the insidious toxicity, denies it, I have shared it...

My personal interest does not come from there, so it is not confined to that. One school of thought envisages a reduction, or even disappearance, of the reservoir. We see from time to time a manipulation exploring latency reversal cocktails or the role of DTG. Latency inversion was my hobby. I did it. In France, I must be the only one! Because, if there is a clique of peroers, there has never been the slightest manipulation. They are reasoners in rocking chairs.

Ananworanich, close-up CVs and FASEB-1

I don't give the same credit to the latency reversal anymore, but I did do what Ananworanich did(first-in-class clinician), with one notable difference: where she has about 30 volunteers, 15 in each arm, I only have one on hand.

We try the cocktail, in double blind, and then we stop the treatment to see if there is a difference in time to rebound. For the moment, NADA... The time to rebound is identical in both arms (intervention and control): 2-3 weeks. The difficulty is not there... We have no clinical support for our legitimate explorations (American veterans do, so it is legitimate and ethical).

That's when I discovered that you can do CV without a prescription! It costs, but, it's possible. Except that... Here's what's not possible: interrupting the treatment and going to the lab to have a CV done on Monday and Wednesday, every week, until it comes back. At that time, the lab's FRAU had warned me: CVs outside of the prescription = OK, but cevetic relentlessness = NEIN. And at the time, the labs that offered this service were not numerous. Today, one could establish a wandering strategy and proceed exactly like Ananworanich...

Except that, here too, the Ananworanich method is not the best: you have to let the virus rise again, then you have to delete it again, which can take a long time and subjects you to the risk of seeing your doctor-secretary change your combo at the same time. Today, with DTG, retreatment is simple and without the threat of resistance. Today I will not hesitate, in fact I did not hesitate to resuppress with DTG as we have seen.

There I discovered FASEB-1, and the possibility to explore the Eclipse, gradually, by small steps. It's much longer, but the pharmaceutical savings(less toxicity) is already a good thing! Even if you fail to go into remission (you wouldn't be alone), you'd have as many boxes of medication left in the cupboard, and that's not bad. Maybe we'll come back to this one day...

My goal is remission!

I've put a little water in my wine and I'll be satisfied with a remission with small feetAt 1/30, I'll stop, it's not a big deal. At 1/30, I'll stop, I promise.

The current philosophy in this matter is anti-scientific: if you stop, the virus will always return and it's not true, we know that now: the Eclipse is and it is 2-3 weeks. In addition, there is a significant proportion of patients in whom replication does not resume until after a month, or even not at all. The alternative, orthogonal, is to say that if you take 7/7, you are sure to remain suppressed, which is also inaccurate: there are exceptions (we may come back to this).

Between these 2 orthogonal propositions, in exact opposition to each other and equally false, there is an unexplored field of possibilities: what happens when you go through a slow withdrawal? That nobody has done, except me: we make X/Y (X can be 1, 2 or 3, we will come back to that) and we extend Y: 7, 10, 12, 14,... 21...

The more we advance, the more we have tools (molecules, CV, tank measurement...) and concordant proofs on the Eclipse. But surprisingly, clinicians are not interested in this: when I talk about it, it's a flop, which proves that Silicianism is deeply rooted in the minds of people who are not known for their sagacity. The world without Peytavin, without Rouzioux and without Siliciano is nevertheless a world full of potentialities, accessible to everyone.

I'm going to 1/12!

My 1/10, in extra-Leibowitchian formula, this time, has been validated. The NFC-3 suits me very well (Charles-Edouard's New Formula!), so we're moving forward, carefully, as usual, and we'll come to complete, without batting an eyelid, new molecules, when the time comes. We are completely free from the goodwill of the medical-pharmaceutical underworldof all those pretentious people who never did anything. Free, finally free... And soon (semi-) cured!

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

131

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



Discovering Islatravir (ep.1)

By Charles-Edouard!

From a well documented veteran:

We've heard it so many times, you'd think the argument was legitimate... It is easy to lose sight of the fact that the aim of a treatment is to cure, not to confine. Especially at the cost of such a devious over-medication, of which one is only really aware after 2/7. Look at what those who take ABC in 2/7 (or even less) say: they complain about it more than those who take it in 7/7. Does this mean we should go back to 7/7? I have never seen anyone go back. The bomb-silence cycle (aka choke-and-mute) creates, as such, a selection pressure that is all the more exploitable and beneficial as the bomb is strong and the silence long. Mini-bomb-mini-silence? Mini-bomb-long-silence? I prefer Maxi-bomb-maxi-silence: my day of liberation is (will be...) the 30th of January 2020. I can't resign myself to life imprisonment, nor to sentence adjustments. Especially since we'll be able to build super-bombs, really well.

Islatravir: Finally the Weekly stamp!

A new chapter in intermittence is opening, and what a chapter it is!

Misconceptions but favorable ones. Believing that one can do 5/7 with EFV, limitingly to 5/7, due to the favorable pharmacokinetics and obvious overdosing of EFV is an original mistake. The first successfully tested intermittence is 7 ON, 7 OFF. The fact that we know how to do the 7 OFF should have opened our eyes to the supra-kinetic character of the cycle. Anyway...

The history of intermittence was built on a misunderstanding, certainly, but it was built. With a very very confidential success. The persistence of the effect of DTG for 3-4 days is registered in the Vidal: patients have started to understand. DTG allowing for 4/7 (or even much less), Dual Therapy and Mono-DTG (not counting DTG-25 mg) opened the Pandora's box to a wider, more receptive audience. With the success that we now recognize to 4/7, with or without DTG, by the way...

And here is: Islatravir. With 2 'favorable'(and antagonistic?) characteristics: It is ultra-nanomolar (EC50 at 50 pmol/l) and it is very persistent. We can afford to put only a very small dose (2 mg?) and the intracellular persistence (of the triphosphate form) lasts a week... at least... Let's bet that the marketing phase will have 2 objectives: to exploit the mini-dose to the full and to mask, as much as possible, the weekly persistence.

Islatravir: a chemist's vision

The story of islatravir deserves to be told, even if it is at the cost of inevitable approximations. Unlike DTG, which was designed by computer, specifically targeting the catalytic pocket of integrase, this discovery was made more by chance and by the intuition of skilled chemists.

In the cost structure of a chemical, the most important contribution is the manufacturing cascade (usually a synthesis). If it is simple, it is inexpensive. To make a nevirapine, take 2 industrial pyridones, mix, precipitate with acid, wash, filter, done. On the part of the industrialist, there is not much intelligence nor deserving work... Let us pass...

But this alone leaves the product unaffordable for the poorest countries. However, to obtain a desired molecule, one could go about it differently: take a complex but cheap molecule and split it to keep only the structure that interests us. Complex molecules at low cost? Yes... vegetable or animal proteins, by-products of the food industry, looking for juicy outlets, and even more, if affinity... We take a cheap protein, we cut it (which requires less energy than assembling it) and if we fall right in the middle, it's bingo! The problem is that we will try dozens of sub-proteins with thousands of potential applications (e.g. egg shampoos), sometimes with a little luck. Originally, an envelope from the JSPS, an agency attached to the Japanese Ministry of Education, to animate institutional university research and facilitate collaboration with industry around amino acids.

A precedent: RALtegravir

Even if there are some notable exceptions (e.g. fosampenavir), the vast majority of molecules useful to pharmacists follow the rule of 5. There are as many possible combinations of C, H, S, N, O and F atoms, which follow Lipinski's rule, as there are stars in the universe: billions of billions. It is like looking for a needle in a haystack. Now, if you have a good hundred thousand... So people like Merck, who have already synthesized so many things, spend their time (and your money...) making trays with little wells, pour in cultured HIV(but also Ebola, Marburg, cancer, whatever) and come and dip a little bit of the AX10295 molecule in one well, then the neighboring AX10296 in another, etc.

It costs a lot of money. Until one day we have a touch. In this case the diketo acid, which has a modest activity but stands out. We look, we study, we create variants, etc. and we arrive at a not too bad drug: Raltegravir (1200 mg anyway!). And a monopoly on the market until the other zozos manage to manipulate the diketo acid to produce something passable (EVG for Gilead and... something as toxic as possible for ViiV, which ended up in the poo, we've already talked about it)

This first touch has, except for extraordinary luck, a mediocre activity: you have to put a huge quantity of it to get the virus out of your well. Not possible for a drug, but it's a starting point. We improve a little, and we only need millimoles, we improve a little and we only need micromoles, we are on the right track. We improve a little more and we hardly need more than nanomole: here is the Grail: we succeeded, we go...

Will ISLATRAVIR kill the 7/7, the 4/7 and even the 1/7?

There is a lot to think about... In a next post: how ISLATRAVIR was conceived and how it can help us break the 1/7 barrier... To be continued, as you will not read this anywhere else...

Obligation of treatment / Judiciarization

- the last straw: Mediator: Servier asks the State to reimburse compensation paid to victims

- Camouflet for the cretinous rouziouists: In France, the (too) early treated give the finger of honor and abandon the treatment in majority. A little common sense in a world of bullies? Too early to stay on track? Shorter time to first antiretroviral treatment is not associated with better continuation of care (here) (sweet euphemism!). This is a FRENCH study! Oh, they didn't tell you about it? Well, let's see...

The only interest in treating (too?) early, in our tropics (cf HIV-CAUSAL cohort), is to be non-contaminating. Obviously, and at the time of PreP (i.e. the shift of responsibility for protection), being non-contaminating is not a decisive argument for everyone... The IST obsession (Everything but Intermittency) is failing after failing and is reaching the end of its logic...

In the news

- The systematic use of dosing in order to adapt to the 'recommended' doses has no effect on undetectability. Another euphemism... Why not say, in good French, that the registered(prescribed?) doses are useless, which is normal, since the concept is biased and the values are false(we will come back to this perhaps). It is in France, but not published in French, and it is here:
In other words, the Morlat dosing recommendations were followed and there was no therapeutic benefit. The concept of threshold dose, in the hands of people who do not understand it (patients and doctors) is a real catastrophe: we could not hope for a better demonstration... It is a FRENCH study! Oh, they didn't tell you about it?Well, let's see...

- Discovery of a second genetic mutation resistant to the AIDS virus: it' s here

Good weekend, good stuffing and not too many drugs ... Right?

130

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



Supersonic Suppression

By Charles-Edouard!

Call unanswered, and for good reason...
Between the ICCARRE, ANRS-4D, Quatuor trials, and the fact that Morlat authorizes 4/7, you have between 1000 and 2000 'official' patients. The ICCARRians' testimony is here, and the others... nowhere... Not one to come and tell about his participation. Not one either to come and tell about a failure, especially as we have been able to highlight the lack of follow-up of the procedure.
The general instruction is to delete again by going back to 7/7, with the same combo. This is with the doctors who 'master' the procedure. There will always be a few who will change the combo, and patients sometimes find this to their advantage. The question of changing or not changing molecules is at the heart of this post.

Close-up CVs: it's essential

I had described here that I had failed the weekly single dose of DTG (150 mg, 1/7). Some readers have come forward and said: 'I can do it'. I believe them. But then again... For me, the use of DTG/3TC in 3/7 or 2/7 (inflated) had already given some warning and the attempt of Mono-DTG (150 mg, 1/7) was a bit of a last try...

Spectacular recovery: I was then displaying my highest CV. On my own, as much as all the other Mono-DTG failures combined! No discussion, but... Shouting resistance would be a bit too fast. With Absolutegravir, you have to expect a rise in CV when the dose is insufficient, a bit like an insulin that is not dosed enough: the objective is not reached, but without prejudice.

By the way, as much as I have a strong opinion on the uselessness of the proviral DNA measurement as a measure of the reservoir(I am therefore an A-Rouziouist), the existence, in my case, of a reservoir capable of restarting the infection is not in doubt. This is an opportunity to challenge some preconceived ideas: one cannot prejudge the height of the rebound(you can imagine that I did not expect this!), nor that one can 'feel' the rebound, as a kind of felt primo-infection(my primo, I remember it, thanks to him...): it is better not to rely too much on the reading of one's body or on luck. Analysis is more useful, as we will see here.

This was the one and only time I deviated from my rule of close CVs (unexpected detention abroad): CV at month-3 instead of month-2. Here again, the lesson is well learned. Afterwards, we do as we can... My new sequence, for example, is, reluctantly, month-1, month-2, month-3, month-6, but it is for professional reasons. So, here, CV at month-3, just after the change to Mono-DTG 150 mg, 1/7, will have been a mistake: might as well remember it!(it may not be Mono-DTG 1/7 that is at fault, we will come back to that). With the years, a certain fatigue to take blood samples every 2 months had been born, by dint of seeing <20 each time. But it is necessary in the initial phase of each change.

Drowning? Recovery? And with what ???

Well... Now you are faced with your $$$ copies (CD4, that's still ok...) and therefore with dilemmas in a drawer: to resume or not the treatment, with or without DTG. Personally, I have full confidence in the long fallow as a method of cleaning up mutants, and do not give any credence to the so-called over-risk of waiting for 350 CD4 as a threshold for resumption(cf SALTO trial, or HIV-CAUSAL cohort). Drowning was an option. Now... Fallowing (1 to 2 years, if you can), then suppression(without DTG, it was long, 18 months, in my case!), then the timid ICCARRian recovery, we took it for 5 years...

So I choose the recovery. But with what? No resistance test at hand. What to do with or without DTG ? Martinez and Lanzafame remove the failures at MONO-DTG and keep DTG. Bart Rijnders, Hocqueloux/Raffi, Katlama, change their approach... We will test if DTG has, for all intents and purposes, behaved like an Absolutegravir.

The virus is smart... So are we!

To the question Cheese or dessert, I often answer Cheese AND dessert! So we're going to develop 2 strategies and combine them.
Strategy 1: Triumeq
Strategy 2: NVP/TDF/F-3TC.

Like the concomitant intake of DTG and NVP leads to a total disappearance of DTGit is useless here. This becomes: combined strategy DTG/ABC/3TC and DTG/TDF/F-3TC, that is, in fact, 2 distinct strategies, combined: namely

Strategy 1: DTG BID 2x50 mg (strong but useless if you are not sensitive to DTG anymore)
Strategy 2: ABC/TDF/3TC (weak, not recommended, but useful in contrast, here).

We will be very attentive to the dynamics of recession. If the descent is slow, we will abandon DTG and quickly put NVP. We will then take note that DTG has become useless. We would regret it a little, but we know how to do the 1/15 without DTG. If DTG is of no use for dynamic remission (1/15 and more), no regrets. If the descent is rapid, we do not change hands, we keep DTG in our remission strategy, but not alone...

Admire the work...

Intake scheme	rhythm	duration	result
DTG/ABC/3TC in the morning DTG/TDF/F-3TC in the evening	7/7	1 month	<20
DTG/TDF/F-3TC	7/7	1 month	<20
DTG/TDF/F-3TC	5/7	1 month	<20
DTG/TDF/F-3TC	4/7	1 month	<20
DTG/TDF/F-3TC	3/7	1 month	<20
DTG/X/TDF/F-3TC	2/7	1 month	<20
NFC-1	1/7	6 months	<20
NFC-2	1/9 then 1/10	6 months	<20 (*)
And in project...		(*): last validated tag
NFC-3	1/12	6 months	start: Sept 2019
NFC-3	1/14	6 months

Supersonic descent offers new perspectives!

It is observed that the virus should have maintained a normal sensitivity to DTG. For a susceptible virus, DTG works equally well at 2 mg, 10 mg, 50 mg, in monotherapy of attack ( ING 111521 trial). It is a methodological error to confuse efficacy and speed(obviously, for a molecule with 1 LOG, e.g. AZT or 3TC, the absence of speed leads to inefficacy, but with DTG we are not in this context). So with 100 mg, on a susceptible virus we should have a very good speed of descent: this was the case. 2 x 50 mg, it's worth it at the initiation, during 1 month, but it's unbearable: depressive effect guaranteed! I endured, but the effect was perfectly visible, what a horror!

If DTG had lost all its efficiency, ABC/TDF/3-TC would have given us a flat kinetic. In the intermediate case, we would have jumped on the way down.

We will never know for sure! But DTG remains in our toolboxwhich is an excellent thing. We'll complete it, for sure, but it stays there. It is ABC that is on the hot seat, and will disappear, phew...

The attentive reader will have noticed that we went from MEGA-Copies to 1/7 in ... 6 months! If with DTG/ABC/3TC/DTG/TDF/F-3TC, 7/7, we did not succeed in the first month, then we could fallow (drown) and then NVP/TDF/F-3TC 7/7. Compared to a fallow (1-2 years)/Tradi-TRI (1 year)/ ICCARRE (4 years) strategy, we win!

Fallowing is the ultimate catch-up net: you have to make sure you have 12 to 24 months to go. Many patients start too early, but if they start when they could have reasonably postponed, it also means that they can afford to fallow. At the time they make the decision, which is too early in our tropics, they are not aware of it, but it comes naturally with time... The exploration of the Eclipse has several nets of catching up. Especially since the close-up CVs are easily accessible and DTG-double dose (or even triple dose) will shoot down any CV in no time. The mega dose to zap the asshole works, of course, what is stupidis to keep the same overdose once the undetectability is reached. This is silly.

And ... Hop!... Forward to the 1/15 (again)

Now, for my descent to 1/15, I'm going slower, since I made the descent to 1/7 in supersonic mode.

In the news

- You are indebted to him and he is dead: Kary Mullis invented PCR, won the Nobel Prize in Chemistry(just that... ). PCR has many applications, including one that concerns you: CV. There is a before and an after to PCR... Dr. Leibowitch, who has always been opposed to double-blind placebo trials, has finally been listened to since he demonstrated the possibility of obtaining an undetectable load(Stalingrad trial in 1995). Before the CV, we went in blind, using the 'guinea pig' patient. No CV, no intermittence...

Once a scientist, always a non-scientist... We make fun of his allegory on the luminescent raccoon, which he commented thus:

Hi, hi, hi...

- Offshoring at the root of the drug shortage in France. Offshoring ??? Ah Bon ??? Does it exist??? Until recently, ARVs were still produced in France. In Auvergne, precisely... And why on earth in Auvergne? Because it was the price to pay to the Chiraquie to obtain the authorizations without too much trouble. Since then, Brussels, Hollande and Macron have been there: nothing grows back!

The French genius

We had exposed, right here, (a little before everyone else...) that the Levothyrox scandal is due to a methodological error: Indeed, one should not compare Mean-to-Mean when the standard deviations are important! Especially not! This allowed us to point out the aberration that is Isentress® 1200 mg(1200 mg! where do they get the idea?) and which has its MA(yes, yes...). This same error occurs in another place in the theory of immediate return(we will come back to this). The re-analysis of the Levothyrox data confirmed the methological error. The authors very explicitly consider that the error was intentional. Le Monde wonders why Merck was overzealous in its evaluation of the new formula.

The multi-year prize goes to the HAS and the health 'authorities' who have been blamed for this sad Levothyrox affair! The mathematical breakdown is here : Why did it take more than 200 subjects to demonstrate the bioequivalence of a new formulation of levothyroxine with an old one?. Didier Concordet, Pierre-Louis Toutain & al. are ... veterinarians ... (from Toulouse). Ah???? Well??? The doctors, where were they? In the Bahamas ??? Well... We are not going to bite the hand that feeds us!

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