It's Achille's, Stupid!

It's Achille's, Stupid!
This paper was originally published here, in French. We provide this translation for your convenience. Some practical aspects may differ where you live.

I found this rather funny:

I love this shortcut: my doctor preferred not to play the sorcerer's apprentice: he added Edurant® .... Contemplating the result: Bravo! What did I not hear about the risk of alleviated treatments. As if adding more (or maintaining too high, it's the same ....) was safer !!! Physicians should take decisions together with patients, after explaining risks. But in practice, does the patient (or doctor) really understands what is at stake?

It is Achilles, stupid!

There are only 2 possibilities: either the risk is random, indiscriminate, or it is unevenly distributed, highest in one group, and therefore, lower or nihil in another.

It is in the best interest of Big Pharma and its relays to make believe that the risk is high and indiscriminate. This does not resist the accounting of known, documented and registered cases.

This is why we can not find anywhere this comprehensive, yet simple, accounting. It is described here: The Achilles heel.

If the risk is random: four failures out of 61 (33 + 28 Barcelona + Paris): 6.5%: it is not high ...

If it is not-random, it is based on risk categories: here, everyone speculates (without any evidence) one says the 'reservoir', this other the 'CD4 count', this one the 'Nadir', that one 'the dose'. Dr. Jacques Leibowitch proves that this is all bullshit. What about C. Katlama's presentation, which provides us very kindly, these parameters, including the historical presence of Achilles' heel? Let's fill the confusion tables, and see which one is the most relevant.

Let's build the confusion table ...

Everyone expresses an opinion on the conditions required before attempting dosage reduction. Most times, this is not consistent with the evidence from clinical trials. For example: make of a good immune reconstitution a necessary requirement: then one comes up with a threshold of CD4 = 350, another 500, another says 800, and why not 2000 while you are at it?

Let fill the confusion table for the criteria 'good restoration' with a threshold of 624 CD4 count (for that is the median, published by C. Katlama EACS-2015, in her trial patient pool).

Is a criterion of good immune reconstitution, before switching to maintenance monotherapy with Tivicay®, effective? NO!

Proponents of this (false) criterion would have excluded half of patients (14), barred, unduly, 13 patients fromt from this strategy beneficial to the patient; They would not have prevented 2 of the 3 failures!

To have a 'criterion' sensitive enough, they should have set the bar at CD4 = 1200; ie virtually exclude everyone! Exclude everyone from a strategy that works for more than 93%: what are they thinking ?!

Well... Who knows of our Parisian virologists will not be surprised.

Fortunately, Pr. C. Katlama saves our face despite this incompetent clique:

The criterion 'Achilles heel' has a sensitivity of 100%.

The criterion 'Achilles heel' has a 100% sensitivity (accounting source C. Katlama EACS-2015)

There is room for improvment, since specificity is only 60%. If we follow blindly this criterion, we unnecessarily exclude 10 of 13 patients, i.e. 75-80%.

Nevertheless, when we put side by side the tables for the (bad) 'criterion' reconstitution and the (good) criterion 'Achilles heel': there is no much room for discussion!

Paraphrasing the famous 'it's the economy, stupid !', and despite being a modestly specific criterion: it is the Achilles heel, stupid !

As for bystanders, leave them to their useless speculations, which are as many superstitions.

Science is the poetry of reality. (Richard Dawkins)

Upcoming posts: How to get a script for 1 year, why avoid the TruLight trial, how to wean antidepressants, dose-reducing doctors ...

Do not hesitate to leave your comments and questions...

Good Weekend and good fuck!


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

Minidolu

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

From one of our regular readers, following our post : Exclusive!

Well reasoned! We are getting there, we are getting there ... Elsewhere, you had never heard of the Achilles heel, HypoDolu, dose reduction by the WHO, Tivicay® monotherapy in First Line, etc. You have never heard of the snowman-melting. Here, we are getting there, and, why not as early as... today!

MiniDolu: dolutegravir 12 mg: 1/4 of a Tivicay ® pill, daily

For about a year, I keep saying that there are only two questions to ask oneself:

1 - Is Tivicay ® monotherapy possible ? and if so, 2 - For maintenance, is 10 mg just as good as 50 mg?

I have validated Hypodolu, once-weekly Tivicay ®, so, the first question, for me, is history: it's in the pocket! (Especially since I was not at risk of the so-called Achilles heel).

For Hypodolu, one question remains: Which dose? As we have no specific guide, and as I can stand it very well, I had opted for 4 pills at one time: so 200 mg: 4 tablets every Sunday.

HypoDolu: makes me very happy! It is so easy! And equally as good as ICCARRE 1/7 (with 4 molecules).

But then, in the meantime, something else happened to me, and I have to take a daily pill for another pathology: 1 daily tablet anyway. Damn ... Before, my weekly Tivicay® was my only constraint. But life is life ...

All the same, only the second question remains :

1 - Tivicay ® monotherapy: is it possible? 2 - For maintenance, is 10 mg as good as 50 mg?

Well, there you go:

So after my analytical interruption (to know my time to rebound ...), I resuppressed the virus with Tivicay® 7/7 50 mg for 15 days. The rebound, which was the whole purpose of the measurement, was very low, so after 15 days, I was undetectable, as usual.

I started with 1/2 of a pill (25 mg) and did a quick validation, then, I moved to 1/4 of a pill, daily.

I put it in a gel-cap along with the other medication I have to take, some sort of 'home-made' co-formulation, and here I am, with my daily intake of the other medication without any visible HIV treatment: 0 intake!

(Let's be honest, the 1/4 Tivicay® pill is hidden in the gel-cap ...)

But still ... it becomes completely invisible.

And a daily 1/4 of a pill amounts to 87.5 mg / week: can't beat that!

And, here I am, with my second VL, under this new strategy, and, still undetectable!

Already three months of experience; I'll just wait 6-9 months and my new baby comes! And since CD4 (1000) and CD4/CD8 ratio (close to 2) are stable, I have no fear ...

Until then, I have lots of new and exciting things

Good Weekend and good fuck!


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

Exclusive

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

I pruned a bit (sorry ...), but this is the spirit:


If you think you or your doctor know how to talk to the virus, you live in delusion: The virus is deaf. Yet, with a good molecule (finally !...) and a good method, it is 'defeated'. The method is conceived from the accumulated evidence and those coming. Opinions, feelings that ignore the evidence are superstition! Don't be afraid ...!

The first line with Tivicay® monotherapy: Exclusive news

This post follows our post on "Tivicay ® monotherapy as induction", where I announced what was foreseeable: Tivicay ® monotherapy as first treatment.

Do not confuse these monotherapy results with maintenance monotherapy (clinical trial: DOMONO) which results are expected late 2016: Congress on HIV Therapy (Glasgow 2016), because of delays in recruitment.

Since the induction monotherapy is for treatment-naïve patients, they do not have the Achille's heel. And all those, who do not have the Achille's heel, are in fact naïve to first generation INSTIs (Isentress® or Stribild® / Genvoya®).

The results are published: this is therefore not, strictly speaking, an exclusive. But since no one has noticed this crucial information, well ... yes ... You hear about it for the first time, here.

Just as you had never heard of Achilles or WHO's approval of Efavirenz 400 mg, it is time to ask yourself some questions about your favorite media!

Lanzafame: the frontrunner!

Dott. Massimiliano Lanzafame?? He is no stranger to us. He appears in this post: "WHO proves us right !". He is to Italy what Leibowitch is to France. His method is a little different, though: he reduces a dose, without any pre-requisite on reservoir, CD4 count, etc. (these prerequisite belong to the 'Parisian', subsidized, bullshit), and demonstrates that efavirenz reduced to 400mg, or nevirapine, reduced to 200 mg, just works as well. No other prerequisite than having undetectable Viral Load for 1 year. Same with Protease Inhibitors.

This is less ambitious than Dr. Leibowitch but Dr. Lanzafame has managed a get his recipe, albeit modest, throught the yoke of international trials and reach, without any reservation, its approval by the WHO. Neither Leibowitch (with his wonderful ICCARRE) nor Katlama (with her shaddy PI monotherapy) ever got even close.

He works in a small hospital (Verona ... That's no New York), so has only few patients: he has good insights, good methods, just a smaller army ! Who cares ? ... Besides we love his way of asking, falsely naively, questions that are of prime importance: If maintenance works with a half dose, then, what use are those famed blood dosage for ? What is it? If not pure bullshit ... I just love it!

Of course, among the small, Peytavin-fed, Parisian clique, he is not popular. But with patients, this working very well. And, let's add, the validation of his Efavirenz 400mg by the WHO (following the ENCORE-1 trial), is really a major success!

So, off he goes, as we did here, with the results of the clinical trial ING 111521, which I commented here.

This trial showed that 90% of patients reach the 400 copies beacon (the final leg to undetectability) in less than 10 days!

Then he will repeat the ING 111521 trial (which dates back to 2008! ...), but, without interrupting at day 10. Same as ING 111521, he goes with 9 patients. The trial ING 111521 protocol required to stop the mono-therapy at day 10 : this time he just goes as far as undetectability... and, obviously, if the VL becomes undetectable, he carries on. There is no reason to stop.

A bit like Dr. Lafeuillade, whose patient by himself, in first line, in primary infection, started with mono Tivicay ® ... and it worked, so why change his regimen.

In my humble opinion, he scored earlier than Salpetriere (a Parisian Hospital)... Blame it on Voltaire, if you want: they'd better move their ass a little faster.

So, our Lanzafame started with 9 patients for first line Tivicay ® monotherapy.

This is far from well greased, slow collusion of our North American clinicians. But where are those Canadians, who had pinpointed the great surprise of the test ING 111521 first ? Not to mention, of course, Dolutegravir's inventors. Here, it is easier to understand: it's a big business. But Canadians? Disqualified, despite having had the pole position?

There you go. It is published here:
http://www.ncbi.nlm.nih.gov/pubmed/27097366
Dolutegravir Monotherapy in HIV-Infected Patients With Naive <100,000 copies / mL HIV RNA Load. It's from Lanzafame (so it's good ... see his résumé); this is with 9 patients, and I will publish the results in a coming post: it's great!

Say, there are only two questions to ask oneself:

1 - is Tivicay ® monotherapy possible, and if so... 2 - for maintenance, is 10 mg as good as 50 mg?

Soon there will be only one left: the second ...

Next posts: Why avoid the TruLight trial, how to wean antidepressants, Yes, This is Achille's !, best doctors ...

Good Weekend and good fuck!


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

Achilles heel

Achilles heel
This paper was originally published here, in French. We provide this translation for your convenience.

Breaking news: I will soon publish the first results obtained with Tivicay ®, alone, in first line ... Bingo!... Bingo!

Certainly, there were rare failures, in some patients, but not just any patient! This is not 20%! Let's stick to data ... The risk is anything but random: it is limited to well discernible patients: those with a predictable weakness: the Achilles heel!

The Achilles heel

Catie discussed in the same issue and Genvoya® and Mono Tivicay ®:
http://www.catie.ca/sites/default/files/tu212b.pdf

Pr. Christine Katlama has drawn attention to the risk to undertake Tivicay monotherapy for patients who already made use of RAL or EVG, i.e. Isentress®, Stribild® or Genvoya®.

Catie presents, verbatim, in English and French, all known cases of failure in this strategy: they are few and well described.

I have presented in previous posts: 1 , 2, 3, and, the original slides are here.

Prof. Christine Katlama divides her 28 patients into 2 subgroups: those who have never taken nor Isentress® nor Stribild® (/ Genvoya®) (Group # 1) and others who have already taken one and / either (group # 2). Thanks to Catie's issue dedicated to Genvoya®, we can do some basic accounting:

In Paris (Katlama) :
Group # 1 Group # 2 + = 28; Group # 1 = 15 and group # 2 = 13
Failures in the group # 1: 0 (15)
Failures in group # 2: 3 (out of 13)
In Barcelona :
Group # 1 Group # 2 + = 33; Group # 1 = and # 2 = group? (But> 2)
Failures in the group # 1: 0 (over ?)
Failures in group # 2: 1 (of at least 2?)

Reading Catie allows us this simple accounting. Just read and count ...

When one is already in group # 2, knowing that there is an identified risk, circumscribed, albeit poorly quantified, and what to do is important.
When one is in group # 1, we can consider to stay there. At least for now.
I am in the group # 1, which appears to date, nice and interesting to preserve.

If you are in the group # 1, stay there ... So avoid Stribild® / Genvoya® at all costs.
The genotype does not help much. These tests were done in patients by Pr. Katlama (of course ...). None had had a previous failure with Integrase inhibitors. This is not an earlier failure that puts you in the group # 2 ... So none of these patients had no detectable, anticipated risk.

Only the patient's history is offered as explanation for the risk..

In group 2, there are three failures, but also 10 success. You can either see the glass 3/4 full or 1/4 empty ... In group 1, no failure ...

Understanding the Achilles Heel is important for all!

There are only two questions to ask oneself:

1 - Is Tivicay ® monotherapy possible, and if so... 2 - for maintenance, is 10 mg as good as 50 mg?

For those who have the Achilles heel, consider your options with care: 4 out of 5 patients are successfull; not bad!
For those who have not (yet) the Achilles heel: avoid it at all costs!
For those who don't have it and will safely move towards the mono Tivicay®, read this carefully: because the risk of failure was the consequence of mutations that you have been able to avoid, then, understand this: it is not because of the dose: the dose (50 mg) was revised upward for all (including those who have the Achilles heel), wheras you were not at risk! QED.

Upcoming posts: Tivicay® Monotherapy in first line, why avoid TruLight trial, how to wean antidepressants ...

Breaking news: I will soon publish the first results obtained with Tivicay ®, alone, in first line ... Bingo!... Bingo!

Have a good week and enjoy sex



This paper was originally published here, in French. We provide this translation for your convenience.

First line monotherapy

This paper was originally published here, in French. We provide this translation for your convenience.

Tivicay ® monotherapy in First Line

By Charles Edouard!

This is thanks to the Internet: we can seek, search, recheck, express ourselves (without censorship ...), identify sock puppets, and disseminate real practical information. Our ultimate judgment is more guided by to the conviction of a doctor, who sometimes earns more in 'consulting fees' than patients visits.

Dolutegravir Monotherapy in First Line (Induction)

In our post: The brilliant Dr Cahn, I had predicted: This quasi monotherapy in treatment as first line opens, obviously, the door to new results in induction monotherapy. This will eventually come out, probably as early as 2016 ...

Well, here we are

I have the results: they are great!

First, let's see what is at stake: the Phase II trial clinical had demonstrated the feasibility of first line monotherapy with Tivicay ®.

For maintenance, there are only two questions to ask, to collectively and individually:

1 - Is Tivicay ® monotherapy possible, and if so? 2 - for maintenance, is 10 mg as good as 50 mg?

For those who start treatment in 2016, or have a virus whithout the Achille's heel (Achille's heel = previous usage of Isentress® or Stribild® / Genvoya®), validation of monotherapy as first line answers positively, obviously, the first question.

Use of Tivicay ® to its true potential means:

- Consider maintenance with less than 50 mg (i.e. 10 mg)
- Use Dolutegravir for PrEP
- Treat better, everywhere: and eradicate

Maintenance requires less than the initial treatment.

What means less than 50 mg (for abatting the initial VL)? What do you think?

Starting in 2016, we will start counting treatment-naïve patients, who become undetectable with Tivicay® monotherapy . They will add to the already 9 known patients (8 in the ING 111521 trial in 2008, 1 at Dr Lafeuillade in 2015. This will add up and reinforce what I have been saying here for some time: monotherapy Tivicay® is a First line treatment, and its logical continuation, for maintenance, is open to an ICCARRian scheme: Hypodolu.

This will also position Tivicay ® Monotherapy against Protease Inhibitors monotherapy, which is already approved by the ANRS (French HIV R&D Authority) for maintenance, but not for first line treatment, where it had failed.

This is expected because the 'power' of Dolutegravir is not only similar to that of Darunavir (approx. 2.5 Log) but probably much more, as I've shown here.

Do not confuse these first line monotherapy results with maintenance monotherapy (clinical trial: DOMONO) whose results are expected in late 2016, due to delays in recruitment.

I will publish, here, soon, the first results of Tivicay ® monotherapy as First Line.

This is a small trial. To begin with...

Generalizing this approach has many merits, especially to make it a more affordable and more attractive treatment.

For us, what matters is that this will allow more patients to enter this therapy for maintenance, and understand, too, that Tivicay ® monotherapy is not a dosage reduction. The dosage adjustment (reduction) is when one cuts into the firstline treatment dosing!

PreP: this will allow to understand that mono Tivicay ® is also a very good candidate for Prep. PrEP is not limited, thankfully, the sole Truvada ®. There is nothing magical about Truvada ® which makes the only technique for PreP! ... And as Aurobindo anounces dolutegravir at $ 66 / patient / year (sic!), well, we can use it also for PreP.

Before considering DOMONO for all, however, one needs to understand the Achille's heel: There is no risk for patients who have never taken nor Isentress® nor Stribild® / Genvoya®: for those took one of these two drugs, there is a small risk: the Achilles heel, which we will explore in the upcoming post, before we publish the full results of the monotherapy Tivicay® , as first line ...

Upcoming topics: the Achille's heel; Why avoid TruLight trail ...

Let us take a pause, and enjoy the taste of this announced victory!


This paper was originally published here, in French. We provide this translation for your convenience.

Reservoir measurements-2

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

Reservoir measurements-2

Reservoir size: # 2 Analytical Interruption

By Charles Edouard!
News Alert: I will soon publish the first results of Tivicay ®, alone, as first line treatment, in treatment naives ... Bingo!

From our friend Lucas (Toulon, France):

The analytical interruption measures the reservoir very accurately. I myself work on it with VL every 2 days ... If I had been treated early, I would have hoped that VL does not come back (... Visconti), but as this was not the case, this will be just to know what day it comes back. I already know that I can go for a week without medication since I do Hypodolu (1/7 in mono Tivicay®) for more than 6 months.

Why analytical interruption?

I recommend reading my earlier post: I describe DNA method reservoir measurement

This measurement has been of no practical use to me. In a cohort, it may be interesting to follow the trend, for example:
- Among early-treated (and Visconti ...), we thus can see the reservoir going down faster, on average.
- In the ICCARRE trial it has been thus confirmed that reservoir is not otherwise affected
- In BIOSANTECH vaccine trial, a significant improvement can be seen.

Individually, no practical information can be drawn from this indicative measurement. On the contrary, measurement of time-to-rebound is very rewarding: it helps know, without risk, when the virus bounces back above detectability threshold. This is useful for:

- Checking BEFORE ICCARRE, if one is a good candidate
- Once in ICCARRE, whether it is borderline or if there is more room
The analytical interruption is different from therapeutic interruption (aka drug holidays). In analytical interruption, Viral Load is monitored frequently and treatment is resumed as soon as the virus shows its face. It therefore leaves the virus no chance to replicate and resume its undermining. This provides a personal and useful data: it can be used to calibrate the ICCARRE reduction.

For most, the time-to-rebound is 10-15 days, making the weekly dosing possible.

Time to rebound at the Hospital

At the hospital, it's simple. You follow the protocol: you stop treatment, and then you show up for a blood test every 2 days. That's all ... As soon as the virus shows back, you resume your same treatment pronto. This method is laborious, is used repeatedly in the reservoir reductions trials and other research. We know that there is not the slightest risk. The resuppression with the same treatment is achieved every time: no exception. At the hospital, it's simple ... But they will probably not offer it to you!

Time to rebound in City without prescription

It's possible! Time to be smart ... You have to anticipate that it may require as many as 5, 10, 20 blood samples.

Obviously, one must master VL without script, which is described here.

It's possible, I did it: it's possible...

That's for one VL ... One must be smart, but again, this is explained in this guide... Your turn.

You're getting there? This is nothing unusual, since I did it.

There, there is a catch: you'll be able to do ONE time, but when you go back two days later, the secretary will see you just did one. Shit! Your plan has been uncovered.

But I managed to do it ... So can you

ICCARRE gave me the idea. Indeed, when you follow ICCARRE 1/7, it is well known that the time to rebound is greater than a week, so it is unnecessary to test the first week! So we will test the second week...

Salami Slicing

We are looking at 3, 6, 9, 12 blood draws, even using a private lab, it will not be easy, we'll start with slicing.
We are going to working week by week, and in each week: Monday-Wednesday-Friday
You do the first week. Validated or not, the virus comes back or not. Then you resume treatment, say 3-4 weeks. Looking at your results, if the virus has picked up on the third day, then, so be it ... It ends there. If the virus has not returned for the first week, we will make a longer interruption and NOT measure the first week: we will measure only the second week.
Treatment is then interrupted (you take no treatment) and no further action during the first week: we will measure Monday, Wednesday, Friday of the Second week, and at the end of the second week (or earlier if necessary) treatment is resumed (say 3-4 weeks). And repeat...

We slice it, week by week, and reduce the problem: we just need to find a solution to have blood draws Monday, Wednesday and Friday.

We do 3 VL in a single week.

By sequencing smartly, we thus arrive, step by step, iteratively to 7, 14, 21, 30 days...

It's a bit long, but we have already simplified the problem to how to do it Monday, Wednesday and Friday.

Vagrancy

There is quite easy: Just go to three different laboratories!

I have successfully used three Parisian labs (belonging to different groups), with results on the web!

This is the basic principle ... In a future post, we will see what to expect and results!

News Alert: I will soon publish the first results of Tivicay ®, alone, as first line treatment, in treatment naives ... Bingo!
Good Night and Good Fuck!

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

A guide to Bitherapies

A guide to Bitherapy

By Charles-Edouard

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

There you go! You have to try hard, but, this iss coming! You have eliminated that big s**t of Tenofovir. That is a huge gain! Now you have everything at hand for future progress: Tivicay® monotherapy and / or short cycle. Keep on the good job!

Why dual therapy? Is it better than monotherapy?

The strategy Triumeq® -> Dual Therapy (Tivicay® based) -> Tivicay® Monotherapy -> 4/7 (mono) and 1/7 (Hypodolu) has a definitive advantage over any other: patients can move forward at their own pace, without bumping into the medical establishment (poisoners in a white coat ...). Once on Tivicay® based Dual Therapy, all doors are open. At the sole discretion of the patient and (possibly, but not necessarily) of their physician.

Door to freedom, the patient's freedom away from the tacit alliance between doctors and pharmaceutical-poisoners-firms, it faces a strong reluctance of poisoners/doctors: this is how we identify them easily.

Dual therapy has a favorable institutional tail wind. See LAMIDOL trial

Commercially, the manufacturer increases their margin by combining a diamond (dolutegravir) with glass beads (eg. Abacavir + Lamivudine) then sells dolutegravir 50% higher!

Hence the idea to change the glass beads from time to time (see the SWORD-1 SWORD-2 trials)

France plays one step ahead and Tivicay® monotherapy gaining ground. Dual Therapy based on Tivicay ® is the entry level option.

Dual therapy based on Tivicay® and other

Here, we discuss Tivicay® based Bitherapies. Indeed, it appears from EACS-2015 and the work by Pr. Katlama (Salpêtrière) that prior use of Raltegravir (or elvitegravir) compromises the chances of switching to dolutegravir monotherapy, which remains our intermediate goal. RALTEGRAVIR (Isentress ®) based Dual therapy should therefore be avoided.

Tivicay® + Emtriva®: our favorite

Emtricitabine is nothing more than fluorinated Lamivudine. Except for one Fluor atom, this is exactly the same molecule ... The name difference between Lamivudine (3TC) and emtricitabine (F-3TC) is confusing.

In practice, we can replace one by the other, without further consideration. The equivalence and interchangeability between the two molecules (the fluoridated, the other not) is recalled in the Morlat report. It is also recalled by the WHO:

Pharmacological and clinical equivalence interchangeability of lamivudine and emtricitabine

It is precisely because it is equivalent, in practice, that trials are conducted with lamivudine (exists as a generic, therefore less expensive). The validity of the very good results also applies to Emtricitabine (Emtriva®) This interchangeability (equivalency) may be misleading. But in fact, it is the same ...

It naturally follows Tivicay® + Truvada (TDF + 3TC-F) and has all the advantages of Tivicay® + Lamivudine. It has another advantage: it will never coformulated.

Tivicay® + Lamivudine (Epivir ®)

: the most popular

Advantages:
- Inexpensive
- No meal obligation
- No known serious side effects
- No specific biological monitoring
- No effects 'psychotic'side effects

Thusfar it is not coformulated, it opens the way for the monotherapy Tivicay®: just leave the Lamivudine on the shelf. This is an excellent transition between the combination therapy and Tivicay® monotherapy. Ideal for ensuring the good tolerability of dolutegravir (Tivicay®) since Lamivudine is considered innocent of everything. Prof. Reynes , who chairs one of COREVIH, is an ardent promoter.

Tivicay® + Edurant ® (Rilpivirine): coformulated but uninspiring

Preliminary tests were conclusive and commercial qualification trials are ongoing (sword1 & sword2).

The future of this combination therapy is anticipated: coformulation (only 1 pill / day.) And FDA approval. As a key holder, a great promotional campaign by the manufacturer: How to promote maintenance of combination therapy without getting the message out that maintenance is done differently than induction (initial treatment)?

So we'll see tons of arguments to explain maintenance in a population thus far held in ignorance.

disadvantages:

- expensive
- meal obligation
- Harmful (Rilpivirine)
- Coformulation (Tivicay® therefore becomes inaccessible)
- Effects 'bizarre psychotic' (almost as frequent as with Atripla)

Tivicay® + Nevirapine: not interesting, stay away

Approximately 10-15% of patients do not tolerate nevirapine. Even if it is tolerated, it has no advantage compared to Tivicay® + Lamivudine. It originates from Raltegravir (Isentress®) + nevirapine (Viramune) Dual Therapy, which had good results, by Raltegravir substitution with Tivicay®, which is more powerful.
We now know that Nevirapine induced a 30% decrease of Tivicay® concentration. It's enough to shy away your basic clinician. (Read here)

You will notice that even a reduced concentration of 30% does not affect the maintenance of undetectability:
the concentration obtained with 50 mg is unnecessarily high for maintenance.

Good weekend and good fuck!


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

Efavirenz 400 mg

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

Efavirenz 400 mg: Dose Reduction

No one is a prophet in his own country...

There you go ... You are right on ...

Efavirenz 400 mg: an history of overdosing

This post follows the WHO recommandation update, presented for the first time in France, in the pst: WHO proves us right!
Everyone has heard about the new WHO recommendations. It was even in mainstream newspapers. Including Prep, launched with great buzz. This one, which will improve the care of millions of patients, the first relief endorsed by WHO, only appears in two lines, and has not been commented anywhere (it can be found here, p.9) .

New recommendation regarding favorite ART (adults and adolescents) authorizes a reduced dose of efavirenz to improve safety and reduce costs.

It is true that when it is necessary to correct the situation, it is hardly glorious!

In first line, Efavirenz from 600 mg to 400 mg.

400 mg ... Why 400? Why not 300 or even 200? Who will remember that in DMP 266-005 trial, the 200 mg worked BETTER than 400 mg or 600 mg. Who decided for 600? It is the manufacturer (DuPont Merck) ... And noone ever questionned this decision. Why 400 and not 500? Because there is a packaging as a 200 mg capsule, so it's convenient for a trial.

In the DMP 266-005 trial, each arm had 36 volunteers: 81% of those receiving 200 mg, compared to 71% of those under 600 mg, achieved < 400 copies / mL, and 2 times more odd effects in the brains have been odserved in the 600 mg group (44% vs. 19% in the 200 mg group).

Why are they doing Phase II trials if we do not take them into account !!!
And what help is a doctor if he does not adjust the dosage ???
As people will remain under treatment for another 10, 20, 30, 40, 50 years, the day will come where they will ask , again: why 400 mg?


Going from 600 mg to 400 mg, saves 0.2 x 365 g / patient / year or 73 grams. There are several million patients using EFV. For 1 million patients this amounts 73 tonnes. Say, 10 years for 10 million patients: 7300 tons!

The initial mistake resulted in a waste of more than 7 300 tonnes of active ingredient!

And, 400 mg (rather than 200 mg) is another waste of 7300 tons of active principle!

Efavirenz ...

Why revisit the recommendation for Efavirenz only? In China 80% of patients are under Nevirapine. In Lanzafame confirms that dose reduction was as effective with Efavirenz and with Nevirapine. After backtracking on EFV (efavirenz, which is found in Atripla), will the WHO draw conclusions and look into other molecules? Or are we going to wait for another 10, 20 years?

TLE-400, FDA & Marketing

Okay ... Do you really think that a system, which failed to make amends and apologize to the victims of Efavirenz 600 mg, and victims of the shortage arising from such wrong dosage, will fix itself ?

No way it will amend itself so that dosage decisions are better thought out.

The FDA will approve the TLE-400, as required for the deployment of this strategy. This strategy is better than EFV-600, but we will, once again, ignore the savings that are possible in maintenance mode, ie the rest of life ... And life is long ...

The FDA will approve TLE-400 ... So, it's only a matter of time that TLE-400 is made available ... But wait... No! They will repeat the DUTREBIS trick, which is duly authorized. Authorized by our agencies, certainly, but not authorized for sales at home!

300 mg instead of 400 mg of raltegravir, this pill exists but you have no legal access to it!

TLE-400 is in the starting block, it even may already be marketed, who knows, and the French pigeons will not be entitled to this NNRTI dose correction nor to the short cycle reduction (ICCARRE).

The oligarchy, locks up the media and you will never hear about it! Let them enjoy skiing in nice resorts and yachting on the Greek coast.

If you find the information and analysis in your media, just let me know! (most lekely you won't!)


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

EACS-2015 Katlama and Genvoya

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

EACS-2015 Katlama and Genvoya

EACS: Katlama and Genvoya®

predictable cul-de-sac:

Bad choice. Stribild ® or Genvoya ® could jeopardize the transition to Tivicay® monotherapy, a gateway to HypoDolu. ICCARRE and ... 1/7 ... well, with this virologist, you are not there yet. Consider virologist change ...

Buzz: Genvoya® could jeopardize Tivicay® monotherapy

Is Dolutegravir (found in Tivicay ® or Triumeq ®) your absolutely perfect molecule, that overcomes all resistance and prognostics? For naïve patients (who have never taken any treatment or those who have taken treatment but not Isentress® nor Stribild® / Genvoya®) this is the case! It's stunning! The SAILING test (previously treated patients with multiple failures) shows a very good success rate but also some failures in patients with mutations on integrase. This looks good almost everywhere, but not everywhere. There is a border somewhere ... Where is it? What about patients who have never failed INI? Does the absence of failure under Isentress® Stribild®, suffice it to anticipate the same overall success as that seen in patients who have never taken these two drugs? At the border, it is not all white or all black.

The border is this presentation Christine Katlama. We find a complete narration in the article by Catie, here. It's long and tedious; transparencies, in English, are more meaningful. Accounting is the same.

Some Patients who had used either Isentress® be Stribild® / Genvoya® failed Tivicay ® monotherapy.
The gray area, it is there: to have (or not) previously used these first generation INIs . Light gray, dark gray, medium gray? This remains to be determined. But one thing is certain: the 3 patients (in Paris, on 13 having already taken Isentress® or Stribild®) and 1 Barcelona will not disappear from the balance sheet.

The gray area is located there, and, this is quite a disappointment for the patients at risk, and a great victory for patients who are not: patients who have never taken neither Isentress® nor Stribild®/Genvoya®, are free of risk they may consider, without reservation, switching to Tivicay ® monotherapy in 7/7, and understand that monotherapy is an effective firstline therapy, and therefore we can later consider the ICCARRE reductions: 6/7, 4 / 7 and 1/7 (= HYPODOLU).

Ah... I feel more educated!

Recommended by a reader: the latest issue of Catie addresses both Genvoya® and Tivicay® monotherapy.
In France, our HAS [High Authority on Health] has issued a very reserved opinion on Stribild®, so we wonder what the ruling will be for Genvoya® (read here and see point # 4):
[...] STRIBILD has not shown improved efficiency, has a low genetic barrier to resistance, many drug interactions [...]

We will keep here proper accounting, accurately and comprehensively of failures induced by the use of old INIS. The HAS [High Authority on Health] was right on: one should have avoided Stribild® (/ Genvoya®)!

Good reading, good weekend and good fuck


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

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

Hypo-Dolu: It works!

Hypo-Dolu: it works!

Read in the comments of the post: Stribild EACS-2015 Hocqueloux

Hypo-Dolu (Hypodolu) is a strategy proposed by Dr. Lafeuillade and introduced here. Use the name of Lafeuillade, a worldwide Hiv celebrity, during your visits: it is better accepted than Leibowitch ...

I first made use of ICCARRE, gradually, 6/7, 5/7, 4/7 and 3/7, 2/7, 1/7 with Leibowitch' quadruple therapy (once-weekly): I am very happy with it, not a single blip. CD4 still high and zero side effects: zero zero zero.

I soon found myself with a stock worth 10 years of treatment (I lost count ...).

I was slyly accused of making business of it, which is not true, but, why not?
Treatment, in a poor country costs 100 Euros per year per patient, and mail it would cost much, so, I gave up. Meanwhile, I realized that I could offer the PreP, of course!
I have everything I need to do it. So, why not do it? We know that this technique works and is approved in the US. 4 Elisa tests (at 24 Euros each, one month apart), a monastic life, cloistered in my sweet home, and now my Lou is free (and me too ... Phew !).

I care about my freedom ... I'm possessive, not selfish ... Freedom not just for me, for others too.

P'tit Lou is free, too ... No reason to change ...

Tivicay® reaches our market (expensive and rare) and Prep is (finally ...) authorized (and free of charge...).

While you are at it, better fill your stock with something useful!

Considering my stock, I am ready for confrontation, if necessary, with my doctor, who has become useless and cumbersome. To my surprise, though, he switches me to Tivicay®. I couldn't care less, I love ICCARRE.

I order Tivicay ® + X . + X is what I care for (for Prep ...), so I'm going to the pharmacy and Tivicay ® is now entering in my stock. Expensive ... and useless ...

I gave Hypo-Dolu some publicity ... And I work on my Guide 4/7, which is now well-crafted. I want to make a guide for 1/7. There are 2 formulas for 1/7: 1/7 ICCARRE with Quadruple Therapy (eg Atripla ® + Ziagen ® in a weekly single dose.) Or HYPODOLU.

Jacques Leibowitch invented ICCARRE method 1/7, and I posted a version in French. There is nothing to add. Just read the patent where quadruple therapy (once-weekly) is explained.

There are many possibilities. In practice, this will be (NVP or EFV) + (TDF) + (ABC) + (3TC or F-3TC, it is the same). His trick just work wonders.

When you do this, you understand that only a VL uptake (monitored every month and then every 2 months) can force you to change your mind. The crying sissies won't stop you... We like the once-weekly!

Hypo-on Dolu is even simpler. The weekly dosing, introduced by Lafeuillade is one pill per week. I'll take more, though, with breakfast on Sundays. And it makes me a weekly dosing; my stock fills up and my doctor regains credibility and usefulness.

Let Lafeuillade publish ... I owe him (and Leibowitch) 2 super effective strategies that will serve me for life.

Dr. Lafeuillade is the head of scientific editorial boards: Use his name and this will open new horizons!

Good weekend and good fuck!


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