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.