123

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relief and intermittence

By Charles-Edouard!

A reader asks the inevitable question:
This is the question everyone will ask... Almost everyone... Others will go for 3/7. It is the purpose of the OMNIBUS project to answer it. Reminder: this blog is not a medical advice

relief vs. intermittence

Since our Staff at the Salpêtrière (Sept. 2018), it is agreed to call lightening, which uses fewer molecules and intermittence, short and ultra-short cycles. Reducing the concentration of EFV from 600 mg to 400 mg (or even 200 mg) has no other name than 'correction of methodological error' .... Obviously, there are people who will want to do both ... Especially since the 4/7 in commercial dual therapy is inevitable... Inevitable, because the only advantage of MK-8591, the EFdA marketed by Merck is its half-life of ... 168 h! To think that the 4/7 in BI will not be done is a nonsense... It is quite legitimate to ask oneself, as of now, the question.

For carefully selected patients, MONO-DTG works very well, and I can assure you that it is very pleasant, since the tablet is very small. I have had it work in half (7/7) and quarter (7/7) tablets! I assure you that when you take your quarter of a tablet in front of a witness, she is amazed... Mono-DTG has a remanence of 3-4 days, it is written in the Vidal, and tested in the ING XXX trial; So people who succeeded in their Mono-DTG in 7/7, went to 4/7, including my excellent friend jesuisdutreize. The weak point of this strategy is that there is an Achilles heel if the virus has been treated, at some point, by RAL or EVG. For those whose virus is old (pre-2007), just look at the prescription history. For the new ones, it is a bit different, because their virus could have been treated (badly) by the person who gave it to them. However, we do not know how to make a relevant genotype for this case, so there is a random risk, all the more so since Isentress ® (RAL) was used liberally, as in Holland or in the West of France...

So, before considering a MONO-DTG in 4/7, one must be sure that one is on the right side of the handle... The passage by 7/7 is thus rather a good idea. It is necessary to be perfectly compliant during this first phase. Then you can work on intermittence, under close biological monitoring, as always. MONO-DTG in 4/7 is great. Today, in Paris, Prof. Katlama is the reference for Mono-DTG.

OMNIBUS-Bicycle

Once we understand the process that leads to MONO-DTG 4/7, we understand better that the process that leads to Bi-DTG 4/7 requires a good real honest validation of DTG/x, in 7/7, for a while. From this point of view, the process is the same, whatever the x in DTG/x: either 3TC, or RPV, or ATV (boosted or not), or nothing. The cause is this Achilles Heel, identified by Katlama and confirmed by subsequent explorations.

Then there is the choice of the second molecule (or not). The undeniable advantage of Mono-DTG is that in case of failure (apart from the Achilles Heel), there is no resistance to DTG. Let's say, in any case, that DTG can continue to be used. Martinez, Lanzafame, and personally, myself, believe that it is enough to reinforce, without making a cross on DTG: that's pretty cool!

3TC: In case of failure under DTG/3TC 4/7, the weak link is not DTG but 3TC, in other words the M184 mutation: this one is a pain... It is easily eliminated by fallowing (1 year off treatment) but you will be bored for the rest of your life and you can say goodbye to dual therapies, to 'classic' intermittence, etc... The objective of DTG/3TC in 4/7 is good if it works, and then what do you do?

RPV: better not to be susceptible to drug-induced depression... DTG on one side, VPN on the other, there are many who can't stand it. As always, if you can handle it, it does, and it's Juluca®, in one pill. If there were no alternative, it would be attractive.

ATV: This is the stuff we're talking about. The highest strength barrier is DTG and ATV is right behind it, so it's concrete. I'm very happy with it, no liver problems, and it's a good way to get to 3/7. Leibowitch and Katlama agree, for once... and consider it for 2/7. That's really cool. Katlama says with booster, Leibo says without...

As long as I have to choose between MONO-DTG 4/7 and DTG/ATV 2/7, for me it's all clear: DTG/ATV 2/7... And there's nothing to stop you from starting MONO-DTG --> MONO-DTG 4/7 --> DTG/ATV 2/7, with Katlama for example.

OMNIBUS-3D

You can also consider, and this is the easiest way, to advance to 3/7 with your Triumeq®, it is eligible for the OMNIBUS-3D trial and so are you, since you are successful in 4/7. OMNIBUS-2D is not yet finalized, but Triumeq® is definitely in! Triumeq® 2/7

My personal experience includes 4/7, 1/7, 1/15 (modified Leibo method), Mono-DTG, in 4/7, in 1/7 (failure), Bi DTG with 3TC or with ATV. The only thing where we have the satisfaction of moving forward is 4/7, 3/7, 2/7, 1/7, etc

Strategy	Toxicity Unit per week	commentary
Bullshit IRR (7/7)	21	if you have shares in Labs...
Bi: DTG + 3TC, 7/7	14	validated (Lamidol)
Any classical IRT 4/7	12	soon outdated?
Bi: DTG + 3TC, 4/7	8	Omnibus-Bicycle, not started
Quadri-Leibo (2/7)	8	rigorously demonstrated, but Videx® unavailable
Mono-DTG 7/7	7	caution (Achilles heel and compliance)
Mono-DTG 4/7	4	caution (Achilles heel and compliance)
Quadri-Leibo (1/7)	4	rigorously proven, but Videx® unavailable
Charles-Edouard formula!	3	new 1/7 (1/15) under exploration

Who to consult

In this case, it's not the doctor that matters, it's the close CVs: if the doctor gives you the prescription, it's free, otherwise it's 70 Euros per CV: not the end of the world... This is the big advantage of Triumeq ® 3/7 or 2/7! You don't have to worry about it! The caution is to make sure that the CVs are close together

That's how I keep the same doctor: he is not at the forefront, that's for sure! In the worst case, no doctor would be suitable for me... Leibo is out of the picture, since he has announced to leave the case(considering his age, it's understandable and inevitable). Katlama, hurry up, retirement is coming soon, but once the plan is made, it's made.

I have published a list of caring doctors, you choose...

Obviously, the alter egos of de Truchis, like Landman or PM Girard, will not be an interesting second opinion for you, it's kif-kif, besides, they are bound by the ANRS trials...

For an enlightened strategic definition Katlama(or maybe Valérie MARTINEZ) at the Salpé, and you also start to take issue with Jean Derouineau, who had the good and nice idea to ask to be part of the list and who does a little bit of everything, in town medicine.

News from Omnibus

It's finally happening! The consultation period around the protocol is coming to an end and it is finalized: we still have to convince some clinicians, and this is well on the way. Well... It's going on... As for the financing, I'm making progress too... Well... Needless to say that the winds are against me, but well... I've just succeeded in an absolutely smoking coup, in a related field, and, moreover, I've been told that the financing is on the right track. And it's a nice funding! I'm going to have the approval letter framed, I'm so happy!

In the news

122

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Toxicity? In your dreams my good lady...

By Charles-Edouard!

Here's one who's had it! One must be quite unconscious!

The worst thing about this sad affair is that there are patients with 800 CD4 before starting a life-threatening treatment. If the U=U is an undeniable benefit of the treatment, it is still necessary to use it! In our tropics, the HIV Causal Cohort clearly shows that there isno excess risk in delaying treatment until 350. The same is true for START, where the excess risk measured is in exact proportion to the participants in the South (where the excess risk is real, as we know thanks to TEMPRANO) and those in the North, where the excess risk is nil, as we must remember. (see my post Early treatment: How Morlat is misleading.

At the very least, he could benefit from the LOTTI trial, which the parrots talk about here, the original article is here. Personally, my natural inclination invites me to treat, but to mistreat in this way the poor basic homo, already an outcast of a society that rejects him, not to mention professional circles, ah bah NO!!!

Toxicity vs. benefit

When the benefit is real or imperfect in the face of a situation of real danger, significant toxicity is acceptable: e.g. AZT, in its time, certain chemotherapies, etc. When the benefit is putative or even illusory, on the other hand, acceptable toxicity cannot be 10-20%, but at most 1-2%. Dr Marc Girard gives us a vitriolic analysis of Gardasil, for which we are still waiting for proof that there is a benefit or that immunization is lasting. Some dream of mass vaccination of young girls (and even young men)... Here, one of the problems is that it is absolutely impossible to identify with certainty a 1% toxicity, but multiplied by the number of innocent girls thus raped, it will make numbers!

In the same vein, let's demonstrate the real benefit of vaccinating infants against an essentially sexual disease, whose immunization duration is only 10-15 years (I speak with full knowledge of the facts, I have been vaccinated, with booster shots, and I keep an eye on them): once they reach the age of risk (say 15-45 years old...) they are no longer immune! The vaccination coverage against hepatitis B in children of 24 months (87% in 2015) is very high, but less than half of the adolescents are vaccinated. And the vaccination of ... infants is mandatory: look for the error! Will we have to wait 40 years to realize that the vaccination of infants has no effect on the incidence? If there was a vaccine against HIV, with an immunization period of 10-15 years at the most, like for HBV, would it occur to you to compulsorily vaccinate the very young?

There are toxic ideas, toxic characters...

When you invite to the debate the Rouzioux ®, the Raffis ®, the Peytavins ® (and I go on...), you spoil it: here are people from whom you have to stay away! I am not even talking about statin spreaders like Danchin ® or Steg ®... And our poor patient, don't you think that a good kick in the ass of his doctor would not be deserved ? Anyway, as soon as you hear Genvoya ®, run away and go read what the transparency commission said about it...

In the news, the French genius

Apparently, there are still a lot of people to pay tribute to him, week after week. I liked the character, even if I buy elsewhere...

overmedication is a chance if you know how to use it!

Comments

Pierre1 March 2019


AnonymousMarch 2, 2019

121

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Sonigo and Darwin: neural pleasure!

By Charles-Edouard!

February 12th: It's Saint Darwin's day!

In my previous post, I put some pretty powerful stuff! First, this picture of the shift from risk and non-risk, which maps the path to remission (Infinite Eclipse): we'll exploit it further. Also that Darwin is the greatest scientist of all time: this has only recently come to my attention. Before, I would have put Copernicus, Galileo, Newton, Einstein or Dirac... It turns out that the problem to be solved, which is here, there, in front of me, is biological and thatone cannot think of biology without Evolution.

Darwin is a man of his time. If it had not been him, it would have been Wallace (whom Darwin himself refers to as a co-inventor). Mendel had already discovered the granularity of heredity (hence the gene). Darwin was already a widely read author, on a par with Dickens, even before 'The Origin of Species'. Let's not make him a hero but a beacon and an inspiration.

There are at least 2 major scientific problems: how to get rid of the virus (or at least its effects) and why it has such a deleterious effect (for a virus so sickly, so slow, so not adapted): once these questions will have been answered, all that will have been said before will appear irremediably false. The Siliciano, Rouzioux and other people who prevented us from cycling in circles, will be ridiculed. Rouzioux will have the double punishment, because notwithstanding her hysteria of the immediate resurgence of the reservoir(invalidated by the analytical interruptions) she will also have argued against the Swiss opinion, delaying as much the inevitable admission of the U=U: as much to say thatit will have ruined the lives of many people!

It is necessary to find another theoretical corpus. Faucy observes and exploits the Eclipse of at least 7 days, Sonigo explains to Leibowich the slow resurgence curve. Charles-Edouard! himself presents Pasteur with the Choke-and-Mute as a workable route to remission(watch the video again!). Darwin took 40 years to perfect his trick: the choke-and-mute needs to be perfected too. It is the basis of dynamic remission, the 1/7, the 1/15. Sorry, it's the attrition (erosion) of the virus (over)life expectancy distribution that counts. Theoretical variants have been presented: Ptolemaic(Leibowitch, the eternal (non)-return), Newtonian(Weinberg, the burial of DNA); there is also the Darwinian(Sonigo, the population burial). The latter is perhaps the most interesting, but rarely well introduced.

Leibowitch tried it in 'En finir avec le Sida', but his chapter with forests and rabbits is unbearable. It comes from Sonigo, co-author of Kupieck, and the story of the rabbits comes from Lokta and Voltera, which I will, one day, demonstrate is the solution to the above problems. This is unbelievable because the allegory is not accessible to the common man, as Evolution and population dynamics is little or badly taught in high school. The West and its medicine remain impregnated with Creationism and Lamarckism.

Pasteurian News

The publication of Asier Sáez-Cirión (Pasteur), that viral persistence occurs in cells with low glycolysis, thus with slow metabolism, has made a lot of media noise. Theannouncement is here, the original article here. So it would be enough to wake them up a little to release the virus and to zap it by tritherapy. Frankly, this obsession with waking up what will inevitably wake up goes against my propensity to sleep in when I feel like it. The Pasteurian news has the remarkable feature of being, in fact, a re-discovery of the fact that the residual virus hides in cells with a low metabolism/rotation (thus long half-life, hi, hi, hi...). Re-discovery then... A discovery of the Golden Boy of Pasteur: Pierre Sonigo. Well... At least this allows us to put the spotlight back on... the rabbits in the forest...

Sonigo comments on this news

Me: The Origin of Species has matured 40 years of epistolary exchanges, always useful in the formation of the scientific idea, to the point that the paternity (therefore the Nobel...) is problematic. I have revealed a bit of OMNIBUS, because I am sure that it will happen, without delay. So, Sonigo graces us with a commentary all the more expensive because he has the rare and fundamental word to the advent of 1/15 (or even better), which is only a matter of time and perseverance. Hidden in this short Sonigo commentary are the pillars of modern biology:carrying capacity, selection by capacity (more subtle than survival-of-the-fitest), a Lokta-Volterra, all concepts that will be explained further. Without further ado, here is the Sonigo-in-the-text, unedited:

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Why OMNIBUS-3D? Because ...

By Charles-Edouard!

OMNIBUS to 1/15: you'll have to be flexible and motivated!

Well... To get as close as possible to remission, you have to be smart! ICARE, the cuckoo with the gummed wings, didn't go very far... It was 2000 years ago!(besides, it is a fable). Today we fly everywhere, including to the moon, and even behind!...

On the road of progress, follow the green boxes, diagonally...

Special feature	5/7	4/7	3/7	2/7	1/7	1/15
broad eligibility
Selection on genotype	No	Yes	Yes	Yes	Yes	Yes
Bi: DTG + 3TC	Yes ?	Yes ?	No?	No ?	No	No
Any conventional TRI	Yes	Yes	No	No	No	No
TRI selected				Yes ?	Yes ?	No
Quadri-Leibo	No	No			Yes ?	No
Charles-Edouard formula!	No	No	No	Yes ?	Yes	Yes ?

A case for OMNIBUS-3D

OMNIBUS is moving forward... The definition of the first component, OMNIBUS-3D, is nearing completion and we are recruiting clinicians and collaborators. To finance it, we will have to apply for funding(grant application) from various organizations. We must be prepared to present the project to decision-makers, who must not miss the substantiated nature of our application. So, we work on a digestible and relevant argument. From there, all variants are possible... The substance of the case is presented here. Once refined, it will be integrated into the financing file.

Argument of the viral dynamics: The Eclipse

HIV infection is chronic. The treatment is in 2 phases: an initiation followed by a maintenance, defined here as starting 6 to 12 months after the undetectability is confirmed. The recorded practice is to extend the initial prescription scheme to the maintenance phase (ref HAS). It is however established (ref Autran) that lymphocyte activation, which is essential for active viral replication, disappears in the 3 to 6 months following undetectability. It has been observed that poor compliance is adverse to the success of the initial treatment and it has also been observed that poor compliance, beyond the initial phase, is not detrimental (ref Lima). Trials of interruption with a view to eventual remission in patients with a favourable profile (SPARTAC trial) or interruption guided by CD4 count (SMART) show an inevitable resurgence of the virus, contrary to the therapeutic objectives. Conversely, analytical interruption trials in patients with a favorable profile (SEARCH 019, ULTRASTOP), as well as in unselected veteran patients ( Rothenberger ref), show a time to rebound (aka Eclipse) of 2 to 3 weeks on average, without it ever being less than 5 days.

The existence of an early reservoir in cells with low turnover/metabolism (ref Pasteur + Sonigo) is the accepted cause of the practical impossibility of obtaining a cure by the classical means of antiretroviral therapy. The latency of the reservoir is maintained by its presence in slow cells. The low dynamics of resurgence, repeatedly observed, and the persistence of the reservoir are two sides of the same coin. We do not know how to purge the reservoir because it has no dynamics, on the other hand, we know how to take advantage of this absence of dynamics.

The first short cycle tests (7 days ON and 7 days OFF) followed by 5/7 tests (Dybul/Faucy test, FOTO) have confirmed this opportunity. The rare failures observed with some combinations, in particular IP, contrast with the renewed success with NNRTI (FOTO, BREATHER): there are rules to discover. The exploration of these rules (FASEB-1) has made it possible to delimit the favorable synergistic combinations, on the one hand, and highlighted the possibility of extending the strategy to 1/7, on the other hand (FASEB-2). The virological failure rate published at the time was 2 per 100 years of treatment, out of a total of more than 10,000 cycles, for the best synergies. These observations, confirmed over time, invalidate the classical pharmacokinetic argument and force a paradigm shift. The appearance of more powerful and more persistent molecules has strengthened the therapeutic arsenal in this respect. As an example, the persistence of the effect, beyond 3-4 days, was observed in the ING 111521 trial (initiation monotherapy with Dolutegravir). So there is also a change in time.

A challenge for EvidenceBased

Medicine
The OMNIBUS family of trials aims to scientifically establish these rules, for the benefit of the greatest number. The supervised practice of 4/7 is now included in the expert recommendations (Morlat report 2017). The robustness of the method is based on 2 observations: the follow-up of the Garches cohort concerns 94 (?) patients and 10,000 cycles; the post-hoc analysis of the 3 failures of the ANRS-4D trial attributes them to the sole failure to follow the regimen: as a result, the intrinsic failure rate is zero (ref de Truchis - Le Figaro). For some, this evidence is not sufficient to consider entering the intermittent treatment with confidence, for others it is an incentive to explore further, without any safeguards and without medicine based on evidence being able to shed any light. The weakness of the evidence in terms of robustness is an obstacle to deployment, and the Quatuor trial only partially compensates for this. Distrust of the medical technostructure has been present since the beginning of the epidemic and is reinforced by the delays and the active debate among patients (Internet, SNS).

Heuristic, Darwinian, incremental, autonomous exploration is within the reach of informed patients who are progressively pushing back their horizon while sharing their success. Academic medicine is challenged to propose eligibility criteria and safeguards. The search for a better modus vivendi is legitimate, in the face of the proposal of pharmaceutical incarceration, early, in perpetuity, perceived as unfair and unjustified. Some people, informed and educated, will be able to do so, while others will be kept away, thus breaking the principle of equality in access to care.

A strong economic incentive

For France, the cost of the salaries is about 1.000.000.000 (1 billion) Euros or 50 Euros per year and per household. At the current rate of contribution, 7 billion of gross salary must be mobilized to finance them, i.e. the salaries of 345,000 people! Arithmetically, each day saved represents a saving of 150 million Euros per year. The delay in the adoption of the 4/7, which appeared quite early in the Morlat recommendations, is detrimental. The validation of 3/7, envisaged by OMNIBUS-3D, in addition to its own gains, will contribute to a faster adoption of 4/7. The gains are therefore greater than the 3/7 strategy alone.

The strategy of reducing Efavirenz from 600 mg to 400 mg results in a saving of 100 million dollars for the CHAI Foundation alone, and already has more than 1 million users (ref Mylan). It is included in the WHO treatment guide. The Quatuor trial will enable the savings to be amplified in areas where the technical means are adequate. The technical means required for the OMNIBUS-3D trial are the same as for the 4/7. All eligible molecules are either free of rights or promised to be widely and inexpensively disseminated in countries in need. 3/7 would therefore represent a 33% increase in savings where 4/7 is deployed.

The financial means provided by donor countries are constantly being eroded while the number of beneficiaries has increased dramatically, following the adoption of the non-distributed treatment strategy. Industrial production capacity is stagnating, depriving 10 million patients of treatment, at the cost of more than one million deaths annually, including 250,000 children and adolescents. Short-cycle strategies will rapidly free up this industrial capacity for the benefit of millions of people: for many countries, this is the only way to achieve the second and third components of the 90-90-90 eradication strategy adopted by WHO.

Arguments against the OMNIBUS-3D trial

Currently, we do not identify any... The 5/7 trials did not identify any limits to the cycles, nor any limitation in terms of molecule (except for the old PIs). If we had stuck to a pure pharmacokinetic vision, without taking into account the pharmacodynamic effect, we would not have dared to try 4/7. The unquestionable success of ANRS-4D shows that it would have been a great mistake not to try to go beyond the pusillanimous 5/7. It would be the same not to undertake OMNIBUS-3D.

In the news

- Lanzafame published 2 articles: Dolutegravir Monotherapy's Virological Efficacy in a Highly Treatment-Experienced Patient and Dolutegravir monotherapy: an option for highly adherent HIV1-infected naive patients [...]: we'll come back to it...

- I wanted to point out a video of a meeting at the LGBT center, posted on: facebook.com/seropotesparis/...
with De Truchis and Landman... Finally, what is more and more amusing: everyone is starting to rally around the idea of ICCARRE. Well, take the time to watch it, we'll discuss it later.

The greatest genius of all

Yes, yes... It's Darwin and soon his birthday... Valentine's day? Well, yes... OK for fun and sex... Why not a Darwin's day? He's the one who freed us from all those bastards... Well... They won't canonize him anyway... Think of making change your treatment, it will be better adapted (hi, hi, hi...)

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Long live 2019!

by Charles-Edouard!

Until 2017, this blog has been collecting and offering available resources on alleviation in general with a focus on ICCARRE, Bitherapies and Mono-DTG. By excluding PI monotherapy, we had made the right choice. Dose reductions, such as A-TRI-WEEK or the half-pill, are of little interest: they are discussed episodically.

Mono-DTG has had its predictable setbacks and its quickest promoters (Bart Rijnders, Hocqueloux) have messed up the work: the Achilles Heel was a trap, they fell into it, head first, and Mono-DTG with them. This is very unfortunate... The Achilles Heel is very easy to avoid but very difficult to admit, especially since we have no simple explanatory mechanism or fine predictor. This leaves us with the only predictor being the therapeutic history of the host (the patient), without forgetting that we do not have the therapeutic history of the previous host.

We will therefore have two schools of thought, those of the usual barkers, who revile Mono-DTG, and those of the virologists (Katlama, Lanzafame, Ottenbuttel) who will manage, year after year, small cohorts totally dazzled by the genius of their prescriber, and stunned by the stupidity (or even the wickedness) of the medico-pharmaceutical underworld. Duly noted.

To ICCARRE, the Gold, to Mono-DTG, the Silver

Since we are dealing with both Mono-DTG and ICCARRE, it was appropriate to highlight the advantages of both. Apart from this blog, no one has taken care to elaborate on the Achilles heel, which puts us well above the pack, in terms of actual service to patients. By ratifying, as early as 2017, the 4/7, the Morlat report, made Quatuor obsolete, and even the official ICCARRE website, left in disarray. The official registration, which is hardly in doubt, at the end of Quatuor, puts an end to the militancy. We had asked the question frankly: does Morlat sign the end of this blog? He signed the end of his translation into Portuguese: our translator understood that it is only a matter of time that the practice of 4/7 percolates to Portugal or Brazil.

We have put online a Practical Guide to 4/7, as early as 2014, as well as a list of doctors: these are, by far, the 2 most downloaded documents, completely unpublished, at the price of minimal maintenance.

As for us, our development continues! We had set the bar quite high: the weekly intake, and beyond.

Now that the 4/7 is achieved, we have to do the same for the 1/7. There is a problem... The 4/7 is accessible to all, at the price of a simple verification on Genotype(and still... ), without distinguishing combinations, reservoirs and other nonsense, at one time agitated by Pr Rouzioux-des-fameux-critères, today put away in the attic. Read the Practical Guide, there is a good chance that you are eligible... But be sure to read it and discuss it with an ad hoc doctor, not just any doctor, please. Don't be fooled by charlatans of all kinds who seek the moral backing of the title of doctor to promote over-medication with invalidated efficacy.

The problem is that some combinations do not work after 3/7. If you are on a proven (Atripla, NVP/TDF/F-3TC) or favorable (Triumeq®) combination, you probably don't understand my concern. The risk is that experimenting without taking into account what we know, we could reproduce the unfortunate case of DOMONO and MONCAY, which would irreparably damage the 3/7. There are prohibited combinations (Kaletra, Isentress) and questionable combinations (probably Stribild®/Genvoya®). Therefore, as soon as there is a vote on a project, the whole clique votes against it and signals, in advance, its hostility. That's how you can recognize a false front.

2018: new concepts

A preliminary step will have been to develop our arguments by supporting them and preempting the usual objections: so we introduce new concepts:

- Eclipse equation (Pastor 05-2018)
- Dynamic remission (Pasteur 05-2018)
- Eclipse statistics (Pasteur 05-2018)
- Choke-and-mute (Pastor 05-2018)
- Distance to remission ( Salpêtrière 09-2018)
- Molecular synergies (Salpêtrière 09-2018, publication to come)
- OMNIBUS (Salpêtrière Sept. 2018)

At the end of 2018, there is a strong argument(the paradigm shift) for the OMNIBUS essays, now written and being refined. These concepts, well argued, are getting a very favorable reception and percolating very well in the all-Paris-that-counts. This is better than denouncing the professors, who are certainly suspected of collusion... Quatuor has put them out of the running.

2018: New tools

As of 2018, we have a modern tool that was previously reserved for professionals: audio-visual presentations. We have taken a cue from the École Normale Supérieure and extended the tool to YouTube portability. Our YouTube channel is starting and 2019 should have a good dozen new presentations.

OMNIBUS is probably the most exciting thing I did in 2018. The website dedicated to it is being tested, it will be available soon...

The trip to Lourdes

The trip to Lourdes? It is the strategy that signs the absence of strategy. Wishful thinking is not a strategy, intermittence is...

This is the main difference between intermittency and lightening: intermittency reduces the active reservoir: this is the choke-and-mute mechanism. The analogy of the lid on the kettle, made popular by Prof. Rouzioux-of-famous-criteria-is-defective, is a deception. No! When you open the lid, the steam does not come out immediately: this is not true.

We don't know how to wake up the tank! However, it inevitably wakes up. So, if you don't know how to wake up the tank, why don't you let it wake up by itself, a little bit, and then slap it in the face and do it again, until you run out. That's a strategy, and we know it works.

The problem goes further: we don't have a remission strategy (although we know, since the Berlin patient, that it is possible) and we don't have an eradication strategy, although we know, since smallpox, that it is possible, or even almost possible for polio, or even, with a little more effort, tuberculosis. We have no strategy to lower the cost, except to relocate jobs to India or China (Bravo!).

Omnibus

Omnibus moves forward... The documentation needed for the OMNIBUS-3D test is written. I let it rest for a while, just to breathe, and I start OMNIBUS-Bicycle.

In the news

- Homeopathy: we finally address the fundamental question: why reimburse a useless 'drug'? The same question will be asked at the end of Quatuor: explain why we have to reimburse the 7/7, which we now know that 3 doses out of 7 are without therapeutic benefit.

- I have added a comparative table to my post on the new dual therapies (see also the discussions in comments)

The genius in video

I'm reposting here links to 2 videos that I find very inspiring: Pr Schinadzi 's (inventor of F-3TC and the HCV cure) and Dr A. Faucy 's on broad spectrum antibodies.

Feel free to comment, like, share and use

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

118

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Blocking storagePar

Charles-Edouard!

Times are hard: not for everyone...

This story of intermittence is the example where the voluntary submission of some (poor 7/7!) makes the joy of the parasites: the medical-pharmaceutical underworld. The submission to the tax of the masses makes the happiness of the beneficiaries of the suppression of the tax. Diesel tax vs ISF. Everyone will have understood. Finally!

Go and participate in the yellow rallies, to get to know each other. What I saw there? A lot of retired people, thirty years old, fathers or mothers of families, very very majority coming from the provinces: they are lost, asking for their way.

A gay activist, or pretended to be one, hostile, came to explain to us that the gay community, and Parisians in the broad sense, hate the yellow vests. Worse, that without the gay community, it is illusory to count on Paris. The lack of Parisian support is glaring, deafening. Just look at these Parisian socialists. Hidalgo talks about the deplorables, a bit like Clinton did in his time. Adios...

The Diesel Tax is a Gay/Bobo Tax

The lack of support from the gay community is sobering... The Diesel tax is a Parisianism: it is a Gay-Friendly tax... No... The Diesel Tax is a Gay-Bobo Tax

For the intermittence, it is also a little the case... The Parisian community, the weekend blowouts under CHEM, preached for their parish and staunchly supported Prof. Molina, who made Ypergay preferable to ANRS-4D. This is not just a personal issue: the 'community' has taken a dislike to intermittence. The community has taken a dislike to intermittence, and it is practiced there: it was the only way to recycle pills before PreP was reimbursed. Now that the little traffic on the rue des Francs Bourgeois has been put to an end, one might have hoped that the community would finally come to the rescue of real patients. This is to forget that the U=U has completely finlandized the seropos, who no longer have a voice in the subsidized associations.

From here, I am the witness of it! My readers are provincial and in parity. And of support, none!

I am doubly aware of this in the preparation/writing of the OMNIBUS-3D essay: a real long-distance and obstacle course. All the more so since, personally, 3D is already far behind me... We'll see... There are things that are progressing well, I'll come back to that... Overall, it's quite positive!

This to underline that the famous 'community' is rather a ball and chain... Just like the consumerist Parisianism is opposed to the yellow vests.

Well... Let's go back to the blockade

Paris was deserted, the distributors empty or barricaded, all the stores wrapped in plywood. Total loss of turnover. Quatar, owner of the 'department stores' and de facto employer of the ruling clique, will not be happy (already that the barrel has dropped by almost 50%). Neither will Hidalgo. Neither will the profiteers of the LGBT distress.

In short, the success was total. Nothing to say. Act V will happen, for sure!

Gassing

The only slogan that was taken up was 'Macron Resignation' and a 'to arms citizens' all the more pathetic because the onlookers were defenseless in front of the rhinos.

The force charged, deliberately, for no apparent reason and caught the lambs in the trap: a blockage at the top, an armored column that around 16:00 goes back up to the pace!

I took a picture of it, petrified as I was between the desire to heroically block the race, and the concern to preserve my projects. The picture doesn't show it, but they are moving forward at full speed: look and count the feet. Never will we have drunk such repression! (see the guilty indifference during the reactionary demonstrations against marriage)

The trap was set, the boulevard, emptied ... A real boulevard for the charge. I recovered the yellow victims a little lower down, quite innocent, an eye cleaner as only relief. They won't let themselves be fooled twice: you can 't clump together in one place, you have to be everywhere and nowhere at the same time.

Storage

This case is not good news, and a call for a general strike would have enough support to disrupt the proper delivery of ARVs, all of which are imported.

Such a signal would do us good! There is no need to go on and on about hoping for the worst: hope is not a strategy. The strategy is to have stock, for yourself and for others. I have stock, for myself and for my friends, only... The obvious lack of support from the 'community' having been well noted.

By the way, I don't take my meds at the pharmacy in the right proportion, but like everyone else: there is nothing to gain by lowering the pressure on a corrupted system. Especially since there is no 'official' accounting that would allow to record the success of the intermittence.

Omnibus

The Omnibus project, validation of the 2/7 and exploration of synergies, is becoming more and more structured. Very soon we will be able to align 4 projects: - Omnibus-3D ; - Omnibus 3-2 ; - Omnibus 3-2-1 ; - Omnibus-bicycle (= 4/7 in Bi). Not too necessary to specify further: the name speaks for itself.
We see a support committee forming!

In the news

- The reimbursed condom!? As long as we have to do it, we might as well do it by halves: it will only be reimbursed at 60%, for one brand only, and it will be necessary to go through the doctor: ideal for PrePistes, probably ineffective for the average male... Can do better' mention

- Very good analysis ofEmmanuel Todd on the Yellow Vests.

The French genius

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97% of patients overmedicated, 22 million without treatment... Let's stop this scandal!

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



The new dual therapies 2018

By Charles-Edouard!

The 2016 bitherapies, now validated

Yes, the 7/7 bitherapies are 'lightening', let's say a de-escalation, made possible with the arrival of DTG. Unlike intermittence, they do not bring you any closer to dynamic remission, unless you validate them in 4/7 mode (or better).

We have already presented DTG/3TC, DTG/RPV, DTG/F-3TC and NVP/RAL. Please read that post. In 2018, DTG/3TC (and a fortiori DTG/F-3TC) and DTG/RPV passed the validation tests, funded by the industry, with flying colors. The result is two co-formulated products: JULUCA ® (DTG/RPV) and soon DTG/3TC which is announced here, following the 2 Gemini trials, with 1400 patients.

Nothing new under the sun and our biotherapies of choice are validated, hurray! Well... Yes, because for patients who do not know the eclipse, the risk was to remain for years and years on superfluous triple therapy. Obviously, it takes the edge off the zinzins like Genvoya® or SYMTUZA® ; the transparency commission (HAS) has also rejected SYMTUZA® and Descovy® by giving them a shitty ASMR... Well...

3 new dual therapies

Today let's highlight 3 new bi-therapies. Indeed, the power of DTG invites clinicians to new approaches, including the question of the relevance of doses or other tricks (boosters)

Nevirapine 200mg + Lamivudine 300mg

Yes, the VerxVe trial shows that the admissible threshold is not 4,000 ng/mL as the Morlatexpert report still claims, without justification(and for good reason...). This leads to this terrible admission, found by chance, on the Saint Antoine assay reports:

In a word, the recommended dose of 4000 Nevirapine(though not whey...) is wrong by at least a factor of 4

Dr. Lanzafame had already reported great success with NVP 200 mg in maintenance. He went further and removed TDF (alternatively ABC), putting his 9 patients on NVP/3TC.

He reports on this in the article here:
'Deep' antiretroviral de-intensification, a strategy to avoid drug interactions and long-term adverse effects of HAART.

Obviously, compared to dynamic remission, this is a pity... But let's think about those millions of patients, often Chinese, on NVP, and who are worried about the use of TDF.

There are solutions, we must explore/validate them

It would be smarter, cheaper and easier to deploy than DTG/3TC, whose favourable price in 'poor' countries is still pending.

Efavirenz 200mg + Lamivudine 300mg: bis repetita and a surprise...

We take the same and we start again: this time with EFV 400 mg then 200 mg, with the suppression of TDF (or ABC): that's what makes you a low cost and low toxicity maintenance biotherapy. A wink to one of our readers who is concerned about this subject.

No need to switch all France from EFV to DTG

Lanzafame remains a pharmacokineticist at heart. Eclipse is not yet his thing, even if he is kind enough to cite ANRS-4D as inspiration, and to write:
The hypothetical effective concentration... My eye!

We ask the great chief of synergies (Aka Leibo) and we learn that Yes! EFV 200 mg is good! and in 1/7 what's more! (with TDF/F-3TC/DDI)... And even better, a patient of African origin (with the right cytochromes) does 1/7 with only 100 mg of EFV (in Quadritherapy)

Lanzafame, by pushing open doors, is not at the end of his surprises!

The end of the end: DTG/ATV, candidate for 2/7 (or even 1/7)

The question is how to use DTG in 1/7: it's not written on the brochure! in Mono-DTG, I don't doubt those who manage to do it; I didn't succeed(I may have made a mistake by putting it in a capsule, go figure...). DTG/3TC in 1/7 does not tempt me too much because in case of failure you get mutation 184, which you then have to clean by drowning. I don't have the time... So I had to find something that fits well... And there ATV is a very good candidate because it is a DTG booster, in addition to being well tolerated, at this homeopathic dosage (1/7...). For Leibowitch, it will be without the booster (ritonavir), so, obviously, it is attractive! The 2 highest barriers to resistance and a pharmacokinetic synergy at stake: here is a good candidate!

We mentioned it during our staff meeting at the Salpêtrière Hospital... And Pr Katlama agreed... So we keep him for OMNIBUS: it's my new hobby! Especially since I'm not done with DTG yet!

In fact, the only thing that bothers me is the DTG/NVP incompatibility: it's irremediable... Well, we'll see with the dodecatherapy, currently being explored, in view of the 1/15.

Finally, to have tried it, this ATV passes finger-in-the-nose: it is really a track to dig.

Bi and intermittence: comparative table

(added on 10/01/19) From DTG, there are 3 Bi options (DTG/RPV, DTG/3TC, DTG/ATV), and the question arises which one is the most favorable to intermittence. Note: the Bi + Intermittence coupling has only been explored by patients, in autonomous mode, or by Leibowitch. To date, the corresponding clinical trials are in preparation (OMNIBUS and OMNIBUS-Bicycle)
From NVP, there are 2 options (NVP/3TC, NVP/RAL). RAL is the source of the Achilles' heel, so it is not to be retained. NVP/3TC remains, published by Lanzafame.

I add (on 10/01/19) a comparative table:

Bi	Pills	Side effect	Cycle Explored	Objective Cycle	led to 2/7 ?	trial planned	preference
DTG/RPV	1	Yes (psy)	not tested	4/7	No	OMNIBUS-Bi
DTG/3TC	1	No	4/7 (stand-alone)	4/7	Yes (*)	OMNIBUS-Bi
DTG/ATV	2	No	2/7 (Leibowitch)	2/7	yes	OMNIBUS-2D
NVP/3TC	2	Rare	No	4/7?	Yes (*)	OMNIBUS-2D
NVP/RAL	4	Yes	No	No	No	No

Yes (*): with TDF added

Charles-Edouard! The Book...

It's not going anywhere, because I'm in charge of OMNIBUS and you can't write history and tell it at the same time, Ah, well... Yes, we can. Well... I don't have time...

In the news

- read this article with interesting data on the Eclipse; it dates from 2015 and has data on a whole population of patients, not only 'top' patients; and the eclipse, relentlessly from 15 to 21 d....

- you can learn a lot from this article: Is dolutegravir pricing fair? A comparative analysis of price and country income level in 52 countries

- another interesting article: Risk of Viral Failure Declines with Duration of Suppression on HAART, Irrespective of Adherence Level: it shows that, after the first 1-2 years, the risk of rebound decreases even with poor adherence: this helps to explain, graphically, why it is necessary to wait for a year of undetectability before starting 4/7

- after the Levothyrox scandal, here is Androcure, and a new brutalization/medicalization of the woman's body.

The French genius

I like Nolween Leroy, here with Renaud Capucon, in the mythical I'm calling you (Bagdad Café)

The prize goes to J.P. Gaultier and his brilliant Freak Show! The ICCARRians will pay attention to every moment: a surprise awaits them, in the form of a wink, which will warm their hearts. Many thanks to our national Jean Paul, of whom we are so proud! See the trailer here, and enjoy it for the holidays!

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