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

2017: our best victories

By Charles-Edouard!

With Hypodolu, we move on to serious things:

I tried 2 Tivicay® + 1 Lamivudine in 1/7. Just peaked at 50 after 3 months ... I do not know what to think ... So I now do 3 Tivicay® in 1/7. We will soon see ... Very recently a reasoned reflection by a specialist raises the question of whether, for the 1/7, the Tivicay® ALONE would not be better, in fact, than accompanied. Indeed, it seems that the pharmacokinetics of Tivicay® ALONE is more favorable ... I'll check ... Happy holidays and let us know!

2017: victory on all fronts

I follow the line of my post: Welcome to 20 ... 1/7

Quatuor

Announced by ANRS in July 2016 (see my post ANRS-Quatuor has started), this very large trial (640 patients) of 4/7 has begun! ANRS took their time! Given the size of the trial, it should not go unnoticed!

Morlat 2017: ICCARRE enters the Hall of Fame

Our ticket: French Guidelines capitulate!: 4/7 is now official in the French recommendations, in conditions similar to trials: it could not be clearer. We even managed to get the message out at IAS-2017, even if it was cut out during editing ... (Of course the battle is not over)

Genvoya® authorized ... An error, in our view

Gilead has lowered his ambitions ... Authorities have authorized a drug that reduces the therapeutic options for alleviation (excluding Mono-DTG, Bi-Cycle, Mono-Cycle, Hypodolu, or 3/7 ICCARRIEN ...) Bravo! If Stribild® / Genvoya® in 4/7 is invalidated by Quatuor (which is quite possible...), what a frustration for patients! If, conversely, it passes, what about 3/7?

The Achilles heel

In our post the ten green bottles, Dr. Blanco confirms, without restriction, our analysis. As long as the suspicion remains, stay away from Isentress®, Stribild® or Genvoya®.

DOMONO

The results of DOMONO have been published. As the authors have avoided an analysis alla Blanco (Achilles heel) it is a total confusion (just read the body of the article). We learn that failures are without prejudice for patients and especially are not the result of a low dosage. We denounced that efficacy is not dependent ONLY on the dose. Since failures are not dose-dependent, it is concluded that the successes are not dose-dependent either. Viral replication only 'sees' 2 things: dose and genetics (of the virus). DOMONO reinforces the hypothesis that efficacy depends on the history of the virus and little on the dose: so if one has a very wild virus, one can modulate the dose. This is precisely what we could do with an Absolutegravir, a concept that allows to understand DOMONO.

Lanzafame

Dr. Lanzafame saves the honor of medicine with his First-line Mono-DTG: work in progress!

Dual-therapies

ViiV will do its best and conquer market share. Juluca® (DTG + RPV) is announced! Paddle and Lamidol have confirmed DTG + 3TC. Results of ACTG A5353 are published: Dolutegravir plus lamivudine as first-line treatment - Perfect! Yet nobody talks about it... Mobidip prefers IP + 3TC ... What will Gilead do?

Leibowitch under spotlights, the Eclipse too!

Dr. Leibowitch has given us a good paper on medical ethics, and Caroline Petit an easy-to-read synthesis (link to the original, in english); the new ICCARRE site is now online (we expect that it will beef up in 2018 ...), which explains why we will discuss ICCARRE less in 2018, and gear up: 1/7 and remission: I already showed that we could go well beyond the banal 1/7. We conceptualized the Eclipse's equation. I even wrote a sketch of dynamic theories: classical, relative and even quantum eclipse (yes ...), but ... Given the lack of scientific reflection on the subject, we are not not in a hurry.

Trump and Big Pharma

Yes! Donald Trump has promised to tackle caviar drug prices! Well... We did not see much...

Transparency

Doctors and patients require less opacity in clinical trials. Trust but check. Our summer series has forestalled all the nonsense we now see about DOMONO. Our readers, duly warned, do not let themselves be fooled. In the same way we will dismount START (summer 2018): we already started with TREMPANO. You are being deceived ... Moreover, you will find here an interesting discussion where an activist defends the idea that it is the responsibility of activists to hide the truth from patients in order to 'protect' the people. To which Dr. Vernazza (author of the Swiss statement) replies that patients have the right to know and that it is not up to the doctor to give a selective presentation.

U = U: finally, a campaign makes a hit

Here is the official website. Associations, including French, fought tooth and nail the Swiss declaration. I will soon post some news. They rallied to it, after years of fighting back, without the slightest mea culpa. Not sure we will forgive them...

Practical Guides

This is the power of this blog: a Practical Guide for 4/7, for Mono-DTG, a list of doctors and, since 2017, a hit parade of drugs and doctors. And a practical tip: the 000 capsule. With that, if you can't manage to progress in your thougths ...

Public health:

There was fear of hatred and of PreP being used in the presidential election: no such thing! It is true that our (French) 'great national debate' has been a distressing void! Well ... Just a reminder: ICCARRE is now in the French recommendations.

My freedom:

Internet has become a megaphone for Fake news. The conditioning of the masses to compulsory vaccination shows that we are also going towards compulsory treatment (for all of us...). Ask yourself a question, at the time of copy / paste quickly: this blog is unique in its content. Why unique? No matter: we win the battle of ideas, lot remains to be done and our progress in 2017 was significant!

In the news

- More than a few hours to replay Cholesterol: the big bluff (or on youtube) otherwise enjoy the discussion in the show 'the scientific method'.

- gene therapy: quick! put me on Delta 32!

- ACTG A5353: A pilot study of dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA < 500,000 copies/mL. That's good, we are making progress... Obviously, these patients will want to aleviate for maintenance ... Well ... Yes ...

Have a good Week, good fuck and do not abuse of meds/drugs

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

Experts Hit Parade - 2017

By Charles-Edouard!

Consequences of poor tritherapies management? Cessation... and... DEATH. The late Kevin Gagneul (†) left us his testimony, which fades into the Web limbos. I find this one: he names his therapies: new light on the question "could he have avoided death by being better cared for?". Can we do it differently and how? (see also here)

Find his videos on Google. He smoked a lot, an aggravating factor: learn your lesson!

His death contradicts the Zeitgeist litany: "treatments are not toxic and well tolerated". My Arse! Here, no 'old' drugs: they are still marketed, very widely used, and apart from marginal improvements, the only real innovation is DTG.

This testimony remains relevant. Looking at the dates, we see that there were already known alternatives (NVP, FOTO, ICCARRE ...). The lucky ones (or the better-off?) already had access to alternative methods, which allowed them to remain under treatment.

Choose an expert doctor

The advantage of ICCARRE is the Autonomous mode, which nothing proves (following simple but imperative rules) its inferiority to the 'medicalized mode', especially if it is... bad!

Our Practical Guide has helped press ANRS, otherwise so slow. And our list of expert doctors gives you access.

After a banal 4/7, we can anticipate inevitable toxicity, go beyond, and visit an expert doctor. Given the almost total absence of offer and medical training, you can visit 20 doctors before finding a good one. Then repeat to find an expert in 4/7, then repeat again for a 3/7, etc. This is the advantage of the autonomous mode. If one whishes, despite any proof, to get 'medical' monitoring, the recursive characteristics of ICCARRE or the specificities of Mono-DTG invite you to go to the best, without wasting time with minons, let alone dummies ...

The caste's interest is to make you believe that one is well worth the other, which, obviously, is false. Your interest is to go to the most knowledgeable.

My practitioner, adulated and acclaimed, refused me 3 times a molecule change. At the third refusal, I understood, without changing my doctor so far: I feel more at home with a veritable Septist, identified as such, than with one whose extent of inexperience is unknown to me .

Trends in 2017

We are caught between a hammer and a hard place: we must help our readers to navigate (see our list of doctors) while the exercise is difficult. I put tendencies to guide somehow: do take this with caution. I'll see if there is a better method in 2018 ...

- The 190: became CEGGID (anonymous test center) ... They do something else ... Just know it: Sharply down
- Dr. P-M Girard: HIV veteran, new to 4/7, enters our list in 2017, slightly up.
- Dr. JY LIOTIER: HIV veteran, does 6/7 and 5/7. His patients are satisfied ... Will you get good advice for a 3/7? Yet to be seen...
- Dr. Leibowitch: IAS-2017 praised him, no less grumpy in 2017 than in 2016, inventor of 1/7: you can't beat that! At the highest (but not for Mono-DTG)
- Dr. Roland Landman: converted to 4/7, co-investigator in Quatuor. Contributes to its diffusion. Beyond ??? To be seen... Slightly up.
- Dr. de Truchis, co-investigator in ANRS-4D and Quatuor. Star without shine, he knows his turf: up!
- Pr. Christine Katlama: her attitude towards ICCARRE is borderline ethical fault (we will come back to this): Sharply down (and not starting from high ...)

Outside Paris

- Dr Hocqueloux (Orleans): Practices Mono-DTG or Bi-DTG, without failure... So, up.
- Pr Reynes Practices Bi-DTG, which will soon be mainstream... Slightly up
- Dr. Lafeuillade (Toulon): Put a name on Hypodolu... Since then... Nothing...
- Dr Raffi (Nantes): mediocre performance at IAS-2017: Sharply down
- Dr. Phillibert (Marseille): HIV veteran, new to 4/7.
- Pr Morlat: not in our list ... He mentions ICCARRE in his 'bible' (without naming it)

Elsewhere

I do not have much info. Dr. Lanzafame (Verona) has taken leadership in Mono-DTG. His paper on Mono-DTG in naive patients saves the honor of medicine. So a very special badge!

In the news

- In the Figaro, it's haro on Luc Montagnier. Remember what Montagnier says: we will come back to it.

- Pierre Henri Gouyon: video: Inate / Acquired, sex / genre and also here: we learn things we will discuss in 2018.

- Lastly, the article on ANRS-4D: Antiretroviral maintenance treatment at four days per week in virologically-controlled HIV-1-infected adults: the ANRS 162-4D trial by Truchis et al. My page on the subject is much more fun!

Have a good Week, good Fuck and do not abuse of meds/drugs

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

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

True and FALSE testimonials

By Charles-Edouard!

False testimonies have poisoned the debate. They always took the form: "I have the friend of a friend who tried the aleviation (eg 5/7) her viral load exploded, she became multi-resistant and waits for her last hour (sic) ". Or a variant ... Whatever, it was always the same pattern, a nauseating rumor. Of course without the slightest detail on the so-called attempt. Partial and second-hand information.

Dr. Cal Cohen, father of FOTO, predicted:

Obviously, there were rules to be worked out.

They are developed from failures: successes do not teach us how to avoid failures.

Now, these kinds of 'testimonies', which would be useful if they were truthful and educated, have completely disappeared. ANRS-4D has nailed them!

This continuous flow, discouraging and irritating, has not dried up at the announcement of ANRS-4D's results, but at trial launch : the mere announcement of a promising trial, has put an end. That's enough to qualify this continuous and nauseating flow as FALSE testimonials ...

Real testimonies and obvious errors

I analyze, here, 2 credible testimonials, which reinforce the rules, difficult to establish, for lack of failures. They are not made for dogs, and one should take them into consideration: read carefully our Practical Guide 4/7 and Practical Guide Mono-DTG.

Painful Failure, under 5/7, with Stribild®

At the time, I had argued against such a double move: switch for Stribild® (out of Viramune®, on top of that...) and move directly to 5/7. The pillars of the experimental ICCARRE are: efficiency, progressivity, frequent VLs. In addition, Leibowitch was up against INIs. My argument was to be very careful with Stribild®. For short cycle, I'm sceptical! First tests with QUATUOR: results in ... 2020!

I argue, I argue ... One thing will stop me: the famous: "My doctor is OK with it and will help me".

It stops me completely: the patient gets a medical follow-up: I am left silent. This thing with medical monitoring always leaves me skeptical given the quality of the profession, however, the argument silences me.

Let's confront this experiment with our Practical Guide 4/7:

Efficiency Verification: Where is it ??? Before entering short cycle, we make sure that the combo is effective, in 7/7, for several months (ANRS-4D: at least 4, Practical Guide at least 6-12)
Progressivity: where is the 6/7 step ???
Frequent VLs: I think that it was done.

Risks identified after ... We could not know beforehand ... The patient is exposed to the so-called Achille's heel risk (previous use of RAL) and to the Quasimodo trap: the transition from Viramune® (NVP) reduces the dose plasma of DTG but also of EVG.

Classical Risks	risk is covered	OK ?	comments
Efficacity	not verified		verify over 4-6 months or more
Progressivity	No		stonestep at 6/7
frequent VL	Yes		at month 1, 2, 4, 6, etc.
less classical risks	risk is understood?		comments
Achille's Heel	No		moreover, EVG is not very powerfull
hunchback trap	No		especially when coming from de NVP
expert follow up	No (?)		go to an expert doctor
results	22.000 copies		but, ICCARRE is not at fault

The catastrophe had been announced: it occurs!

Rightly so, you should not believe everything you read about aleviation

Here, the testimony is incomplete and (intentionally?) false

Here is the sequence. Very early (too early?), Dr. Bart Rijnders launches the DOMONO trial: everyone is very excited (too much?) by DOMONO: a trial without specific conditions to inclusion and with a comparator arm: the must-have. At first everything goes well and the news leaks out, which encourages more. While DOMONO has already started, Prof. Katlama announces, in a conference, that he has identified a major risk factor: Achilles' Heel: a clear risk if RAL or EVG has been used in the past. B. Rijnders continues, ignoring it.

Conversely, I warn as best as I can do, especially our witness (sauvenière). It exhausts me, because it is unexpected, difficult to explain, to understand and difficult to admit.

The 'witness', in denial, has an Achilles as big as the nose in the face: he comes from "Viramune® and Isentress®" (Again ...), in long-term success. More Achilles' Heel than that, you die! I insist then falls the (in)famous: "My doctor is OK with it and will help me".

All this is perfectly archived ... Then, Dr. José Blanco, in his presentation at CROI 2017, confirms our analysis. B. Rijnders refuses to revisit the data of his cohort and his protocol: the disaster is no surprise! It was not possible to know at launch of DOMONO, then, it became obvious during its course: the trial is invalid.

Our witness (sauvenière) lies when he says that he was well accompanied (no frequent VLs ...) and had the righrt profile. In fact, he had the worst profile, and he knew it. Victim of his own negligence, he prefers to accuse the strategy, rather than his imprudence: a scenario for Dr. House.

The nauseating medico-pharmaceutical mob will immediately rush into the breach.

Let's confront with our Practical Guide Mono-DTG

identified risks	risque is understood?	OK ?	comments
Achille's Heel	No		Beware of an history of RAL or EVG use!
Hunchback trap	No		double DTG for a few weeks
frequent VLs	No		Blood draw at month 1, 2, 4, 6
Adherance	yes		in experimental mode , this is important
expert help	No (?)		choose expert help
Result	rebound at 1000 copies		but, Mono-DTG, well understood, is not at fault

A Good Practical Guide vs a bad doctor

In both cases, there is poor medical advice. Despite the absence of a Therapeutic Guide, a medicalized ICCARRE deploys in Maghreb, where doctors receive a 'training' full of errors! So, now, there is a risk due to poor medical monitoring. They CLAIM that ICCARRE will be medicalized or will not be WITHOUT quality medical training or Therapeutic Guide, so, we must expect the worst! Patients are more than ever on their own!

In the news

- The new site the Friends of ICCARRE is online! At long last!!!
- An interesting lecture by Dr. Arvieux on Youtube highlights the misallocation of budgetary resources: a very PRO-ICCARRE argument! (partial slides here)

- Dr. Dupagne explains: the discordant doctor is excluded from the scientific debate and becomes non-grata conferences! In Arte-Replay or on his blog

- These killer mini-drones made the buzz

- A choreographer dances for ICCARRE

- a controversy opens (finally!) on the actual contents of the reservoir ... To be continued ...

Have a good WeekEnd, good fuck and do not abuse of meds/drugs

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Have a good Week, good fuck and do not abuse of meds/drugs

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

One capsule once a week

One capsule once a week

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

A single cap for a single dose (2/7 or 1/7)

By Charles-Edouard!

A comment read on our post : 1/2

In maintenance, one can question the relevance of a daily Truvada®; with the arrival of Mylan's Truvada ® generic, and soon of Atripla ®, you can discuss the daily half-pill.

Here comes the Great Single Capsule !!!

The trick: the Triple Zero 000 capsule

Just type "Triple Zero Capsule" or "empty capsules 000" in Amazon. Direct link. Or ask your pharmacist. The capsule dissolves immediately and completely in the stomach.

Here with 2 x Tivicay® + Lamivudine. It also works with 1 x Tenvir or Viread® (TDF) and probably generic Truvada®.

I am at 2 x 50 mg DTG + 300 mg 3TC, 1/7; With the fall, I caught something, and the 3-month VL raised just above 50. Not enough to scare me: I play safe: 15j. in 7/7, then 15j. with single capsule 3 x 50 mg DTG (Wednesday and Saturday). Then I will carry on with a single capsule 3 x 50 mg DTG, in 1/7, Saturday, with meal, and VL 1 month later.

A 100 capsules pack (2 years, taken weekly) will cost you $ 10 (including shipping); a 1000 pack (3 years in 7/7): $ 30; So between $ 1.5 and $ 10 a year!

Generic of Truvada® = the end of Triumeq® ?

As the generic of Truvada® (Mylan) is 179 euros, instead of 406 euros, this combo TenofovirDF / emtricitabine (Ge) + Tivicay® (dolutegravir) is at 788 euros instead of Triumeq® (ABC / 3TC / DTG ) at 928: one saves 140 Euros per month and avoids the calamitous Abacavir. 1600 Eu Less / year!

Tivicay® + Truvada® was the most expensive: this is no longer true, thanks to the generic, and with the 000, we regain the comfort of a single capsule.

Generic, ric, ric, ric

The inside diameter of 000 fits exactly that of Tivicay®, and then, you complete; Done with opening several boxes, or asking oneself "Did I forgot X or Y": for $ 5 you can enjoy again the comfort so much praised by BigPharma and their collaborators!

The ICCARRIAN veterans are still dreaming of an all-in-one Quadritherapy: For us, it's solved! Is this trick of interest to you? Thanks for sharing your experience!

Have a good Week, good fuck and do not abuse of meds/drugs

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Have a good Week, good fuck and do not abuse of meds/drugs

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

Wainberg and his lone mouse

By Charles-Edouard!

Our reader Colibri testifies, right on:

The recursive principle makes remission, albeit partial, possible only as an extension of 1/7. And the power of DTG is favorable! Thank you for this testimony !!!

Short of an history of RAL or EVG, no resistance with DTG

The French database has very little resistance data on DTG, and the only known resistances are those that appeared during the Viking trial or similar (in multiple failed patients, including RAL / EVG) and the Katlama trial (EACS 2015, which demonstrated the Achille's Heel).

NO resistance mutation EXCEPT for prior exposure or failure to RAL or EVG. ZeRo, ZeRo, ZeRo. Dixit A. Marcelin (Webcast O332, Glasgow 2016, and PS3 / 1, 16th EAC, 2017):

In France, there has never been evidence of any mutation of resistance to DTG. Except, in patients pre-exposed to RAL or EVG. One will be wary of RAL or EVG which can lead to a reduction of therapeutic options (DTG or Bictegravir).

To claim that Mono-DTG does not work, with no consideration for the Achille's Heel, is an imbecility of the first order. More stupid than that, i have never seen: Dr. Marta BUZZI (abstr. PS1 / 2) pools the wool everyone's eyes, throws the baby out with the bath water, writes a stupid 'meta-analysis' that mixes patients with Achille's heel (high risk) and patients unaffected, which, of course, falsify the outcome. And I spare you all the idiots who echo it!

Mono-DTG in the humanized mouse

Mark Wainberg was the ardent ambassador of a miraculous DTG that was free of resistance. His prediction, already old, prior to the trials, was, for short, that Mono-DTG would work well on naive patients, rather well in the preexposed patient, and not too much in the patients with prior failure (in particular, failure to RAL or EVG).

To validate this prediction, one would need some clinicians to get to it.

Big Pharma sponsored clinicians? Do not count on them! The choice is thus very limited ... There are no many candidates... So, our good Dr Wainberg undertakes to convince the clinic that it would be interesting to try Mono-DTG on naive patients and will mount an experiment with an animal model: the humanized mouse. It is lesser than primates and also cheaper.

The green mouse: a pre-scientific fable

An old French, strange, Nursery rhyme that dates back from a pre-Darwinian era (see : Mary Had a Little Lamb). Read on Wikipedia or see the video:

A green mouse
Who ran in the grass
I catch her by the tail,
I show her to these gentlemen
These gentlemen tell me:
Dip her in oil,
Dip her in water,
She will become a snail, all hot.

A hastily conclusion

If we limit ourselves to the conclusion, here, we read: We show that Dolutegravir as monotherapy is not sufficient to maintain the suppression of HIV and that resistance mutations differ from those reported in tissue culture experiments.

Holy Shit, here we are in despair!

A closer look (which nobody ever takes...) shows that among the 5 mice, treated in Mono-DTG, only one fails. Let's look closer:

The mice have very high initial VLs (> 100,000): they are small animals. The effectiveness of mono-DTG, depends on the dose AND the initial viral load. However, the dose for the mouse is calculated according to a heuristic formula. In general they divide by 12, here they divided by 70 ... We can therefore fear that the dose is, all things being equal, a little low. In fact, serum levels are similar to what is found in humans. It is observed that the serum dose of the mouse that fails is 50% lower than the others ...

The mouse that crushes our Mono-DTG dreams has two adverse and combined characteristics: high VL and low DTG dose.

Fortunately, Lanzafame saves the day

Mixing high-risk patients and others is mediocre medicine.

In contrast to Dr. Buzzi who, shamelessly, mixed patients at risk (Achille's heel) with patients without risk, Dr. Lanzafame works in the favorable quadran: moderate VL (<100,000) and standard dose.

Wainberg validated	Wainberg's Forecast	Clinical results	Clinical trial	Forecast Quality
patients with failure	so-so	so-so	Viking
Maintenance 1	rather good	rather good	BMM+P
Maintenance 2	good	good	BMM+P (except. AH)
naïve patients	Good	Good	Lanzafame

Like everyone else, he understands Wainberg's prediction, and embarks on Mono-DTG starting with the most favorable patients: those with low VL. Dr. Pedro Cahn did the same with his patients whose VL was <20,000 under DTG / 3TC.

In the news

- FDA authorizes a compliance snitch. Treatment obligation is getting closer!

- Excessive indication extension: At 130 you are in hypertension! Americans are morons!

- Innovative proposal by N. Chomont: target the reservoir right at primo-infection. Lots of trouble whereas we have a simpler and more effective method: Cycling (we will get back to it...)

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an excellent article

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

An excellent article by Carole Petit

Brought to you and commented by Charles-Edouard!

Note added 08 Jan. 2018: the Conversation has since published an English version

HIV: soon the end of daily treatment for HIV-positive people?

By Caroline Petit, École Normale Supérieure (ENS)

A pillbox (photo illustration). Shutterstock

Most HIV-positive people in France take daily treatment for life. But the possibility of easing this constraint is looming for patients on triple therapy, i.e. more than 100,000 people (France). A major trial began in September 2017 [translator's Note: English here] to confirm, in the continuation of a smaller trial, that patients can skip several [Note: consecutive] days of treatment in the week without risk to their health.

In France, some 300 patients have already switched to a "intermittent short-cycle" treatment method. For years, they have taken their medication four [Note: consecutive] days a week, instead of the seven days as per official protocol. And they are doing well.

The new trial, named Quatuor, was launched by ANRS, the French Agency for Research on HIV / AIDS and Viral Hepatitis. It aims to show that there is a benefit for the patient to take his triple therapy only four days out of seven, compared to seven days out of seven. 640 volunteers are being recruited [translator's Note: English here] in the 65 public hospitals involved in France, including the Caribbean. Dr. Pierre de Truchis, infectiologist at Raymond Poincaré Hospital in Garches (Hauts-de-Seine), is the principal investigator of this trial.

It can be assumed, however, that physicians will not wait for the results of this study to suggest to some of their patients remove three days of medication per week. The prescribing recommendations published in May 2017 [translator's Note: English here] for the medical care of people living with HIV, under the aegis of the National AIDS and Hepatitis Council (CNS) and the ANRS, go in this direction. "On a case-by-case basis, under conditions similar to those of the studies carried out, a strategy of intermittent take four or five days out of seven can be considered," say - cautiously - the experts. It should be emphasized that such a change implies a rigorous medical follow-up, with close biological examinations.

Fifteen years in favor of treatment four days a week

There is now a 15-year expertize in the safety of intermittent aleviated maintenance therapy. The main experiment is conducted since 2003 as part of a protocol called ICCARRE, an acronym for "intermittent in short cycles, anti-retroviral remain effective". This program was initiated by Dr. Jacques Leibowitch, a known figure in the fight against HIV / AIDS. He was the instigator, in France, of tritherapy which, in 1996, transformed a mortal pathology into a chronic affection.

Patients followed by Dr. Leibowitch and his colleagues at the Raymond Poincaré Hospital have thus gone from seven to five days of treatment a week, then to four. In spite of this, their viral load remained below the detection level. These results for 48 patients were considered sufficiently robust by the international scientific community to be published in 2010 in the Faseb Journal. The same experiment led to a second publication in 2015, with a greater number of patients (94, precisely) and more years of hindsight.

That year, the direction of Assistance Publique-Hôpitaux de Paris (AP-HP) and Versailles Saint-Quentin University, the two employers of Dr. Leibowitch, jointly invested in the filing of two international patents , one for so-called "maintenance" tritherapies at four days a week and less [translator's Note: English Patent_US20120283177], and the other for the use of innovative quadruple therapies for this purpose[translator's Note: English patent_US20120270828].

A first clinical trial nationwide

Convinced by the first results of the Iccarre protocol, ANRS launched in 2014 a two-year clinical trial conducted in 17 centers in France, named 4D (English, four days). The doctors received many applications to participate in this trial, to the point that they had to refuse, as entrusted to me by Professor Christian Perronne, the principal investigator. The findings were presented at the 2016 International AIDS Conference in Durban, South Africa [translator's Note: English poster]. They indicate that 96 of the 100 patients in the trial who followed the dosing regimen with four consecutive days out of seven did so successfully. 3 patients had a new detectable viral load by the fourth week of the study. It has become undetectable again, with the return to a daily treatment regimen. 1 patient left the study.

The results encouraged the ANRS to continue in this direction with the Quatuor trial. The new study has, this time, a "control" group consisting of patients who will continue to take their treatment seven days out of seven for 48 weeks, to allow for a comparison. This methodology meets the requirements of health authorities for the level of evidence to be provided before a change in their prescribing recommendations.

"Quartuor seeks to demonstrate that the four-day-seven strategy is non-inferior to the seven-day-seven strategy, in other words that at equal effectiveness, patients in the Aleviation group will get secondary benefits from this protocol. 'side effects, better compliance ...)', said the ANRS on September 1 on its website.

Daily treatment, sometimes badly perceived

In fact, the stress of taking a daily treatment can be a bad experience. Many patients are less regular in their dosings after several years of treatment - a problem for many chronic diseases. It is very risky for patients to reduce their own treatment without medical supervision. [Translator's Note: this is a statement which we oppose]

In addition, the use of anti-retroviral drugs is sometimes accompanied by side effects such as nausea and diarrhea, as well as fatigue. Dosing reduction can be accompanied by a reduction in these effects.

Switching to four [Note: consecutive] days a week is the equivalent of five months without medication for the patient.

What will happen now? It is only after the results of the Quatuor trial, at the earliest in 2019, that the practice of four days out of seven can officially be recommended in France. [Translator's Note: it is, in fact, already recommanded - Morlat 2016 - at time of this translation] Abroad, it has not drawn much interest. Not even in the United States, the country that initiated first, in 2001, a path to Short Cycle that Dr. Jacques Leibowitch had followed.

It is surprising that this reduction in treatment is still, more than fifteen years later, at the experimental stage.

It must be said that in France, the historical patients associations in HIV / AIDS have not grasped this issue. They focused on other priorities such as preventive treatments, pre-exposure prophylaxis (PreP). On the other hand, patients of Dr. Leibowitch following a lighter treatment created an association, The Friends of Iccarre, under the impetus of artist Richard Cross. It aims to promote intermittent therapeutic aleviation for all [translator's Note: English abstract].

The doctor free to prescribe according to the code of medical ethics

Only a few AIDS clinicians in France have begun to aleviate their prescriptions. Article 8 of the code of medical ethics allows them: "Within the limits fixed by the law and taking into account the acquired data of the science, a doctor is free of his prescriptions which will be those which he considers the most appropriate in the circumstance".

The persistence of the seven days a week regime can be explained, in my opinion, by a resistance to change - which is not unique to physicians - and by the difficulty of challenging a long-standing rule in the medical community. One can imagine that other factors at play: obviously, patients prudence and of doctors before a level of proof considered as insufficient according to the standards in force; the fear of doctors regarding the judiciarization of medicine; or the influence of the pharmaceutical industry on the strategic choices by medical authorities.

Seven to four days of treatment represents 42% fewer drugs. This would result in savings of around 500 million euros for the French health system each year (based on 100,000 patients on treatment, with an average cost per patient and per month of 1,000 euros on average). Globally, the issue of cost meets ethical and humanitarian concerns at a time when 22 million HIV-positive people still do not access triple therapy.

For his part, Dr. Jacques Leibowitch pushes further the alleviation of treatments, in accordance with the code of medical ethics, and for patients who so wish. It reduces medication, depending on the case, to three, two or a day only a week. With this new protocol called "big" Iccarre, he pursues the goal of finding for each patient the right dose, both necessary and sufficient. In accordance with The principle: Primum non nocere ("first do no harm") which was dear to Hippocrates?

Caroline Petit, Biologist, CNRS researcher at IHEST, École Normale Supérieure (ENS)

The original version of this article was published on The Conversation.

1/2

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

The amazing and promising 1/2

By Charles-Edouard!

In comments, a Genvoya® not innocent at all!

This example shows how younger people are wrong not to worry about long-term toxicity, in advance. With age comes also polypharmacy (eg statins, useless but often prescribed). Now, Genvoya® has a non-exclusive booster: it is included and boosts one of our other drugs and thus we are in overdose. This also highlights a low noise, sub-clinical, but very real, toxicity.

1/2 = half-dose or 1 day out of 2?

1/2 comes from community practice, not academic. It results from a pharmacokinetic vision, complementary to the Eclipse. Many do not understand Eclipse.

So be it... The 1/2 does not lead to remission. On the other hand, it is understandable by the Septists, that is to say 99.999% of doctors and patients. Pharmacokinetics at heart, they practice it with permissive drugs (eg Triumeq®, Atripla®). And with long lifetimes, taking 1/2 pill each day or 1 pill every 2 days is quite similar; The 1/2 is a dosage adjustment. This is the A-TRI-WEEK trial, which worked very well!

I have done Mono-DTG: 1/4 of a pill (mini-Dolu), others are doing Mono-DTG 1/2 of a pill (or even Mono-IP 1/2 dose). Certainly, my preference remains for the short cycle. I liked reduced dosage also!

Efavirenz 300 mg? Why not?

In the Phase II trial (DMP-266-005, by Joel Gallant et al., Never published ...), 200 mg works better than 400 mg and 600 mg ... And what do they chose? Well ... They didn't care ... 600 mg and fuck you all! Dosage is the responsibility of doctors, not of the pharmaceutical industry ... Facing a suicide epidemic, smart people tried EFV 400 mg: it works. For some unknown reason no one tried EFV 200 mg ...Go figure ...

At the IAS 2017 conference (video here), at minute 49:25, Pr Kiat Ruxrungtham, says: we do with 300 mg and it works very well... Here is a good idea! 300 mg !!!

Note, incidentally, in this sequence, something interesting: they have done tests and offered to patients who have CNS problems with EFV 600 mg to reduce down to 400 mg without even a dosage. And it works ... Which leads him to say, in the same wake, that it also works at 300 mg. Question: If it works without problem at 300 mg, why restrict oneself to patients complaining of CNS problems only?

What synergy???

Phase II data is available here: Dose Optimisation: A Strategy to Improve Tolerability and Lower Antiretroviral Drug Prices, by Hill, Ananworanich, and ... Calmy! (Sic)

Synergy, a heuristic concept, with no identified mechanism, claims that some combinations work better than others. However, the dosage is never reconsidered. Thus, 3TC is set at 300 mg from its early introduction. It dates back to AZT / 3TC Bi-Therapies. Nobody ever had a commense reflection: well, with Efavirenz, maybe we can reduce 3TC a bit. As If ... There are some clever people, who have seen that Cobicistat (an hepatic metabolism inhibitor, often named: EVG booster) ALSO boosts TDF, and ask the question why do not we reduce the amount of TDF at the same time? Simple, doing so it brings not profit to Gilead.

There you go: Effect of cobicistat on TDF: what is true for TAF may also be true for TDF

Especially since they will effectively reduce when switching to TAF. And may be, they already have a me-too copy of 3TC (I bet you they will add another Fluor), some sort of 2F-3TC, that they will come out of their magic hat and market as an all new combo, less dosed.

And no one to look back and say, "Oh, but we used 3TC abusively, at 300 mg, for years without asking any questions."

300 mg EFV + 150 TDF + 100 F-3TC: a poor man's Caviar

It is clear that, today, patients are very well treated in Thailand, probably better than at home! Intelligence is not reserved for us. So Siamese or Chinese clinicians will uncover the hidden Gral: they are at work there, without you noticing. Then will appear a combo composed of 300 mg EFV + 150 TDF + 100 F-3TC (or 150 3TC), to take twice daily for 1 year, followed by 1 per day ad-vitam. Maybe even 200 mg EFV ... Why not?

And we can only then note, once again, the inanity of the ANRS. We have no ideas, they say. Yet, alternative proposals are moving forward.

You will be fattened with injectables at 10,000 Euros per year, whereas they will have nice and effective treatments at 50 Eu / year. That is crazy! After we are being told that French workers are not profitable, they are lazy! So they cut jobs, cut jobs, cut jobs ...

No need to go to Thailand: sooner than never, Greeks, Ukrainians, Cubans, Venezuelans will get at it.

In the news ...

Does Prep flops? Only 5,000 Prep users! Activists are highly disappointed! So they go at it again ...

Interesting article by Carole Petit: puI'll publish a translation real soon!

Universal, mandatory vaccination is voted: when will come mandatory treatment? Not before the arrival of injectables... So this is coming. Here again subsidized Seronegative activists will be at work!


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Have a good Week, good fuck and do not abuse of meds/drugs