122

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



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

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



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:

120

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



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...)

Feel free to comment, like, share and use