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Sunday, April 24, 2016

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.

Saturday, April 9, 2016

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

HYPO-DOLU EACS 2015 Dolulam Dolutegravir Dr jacques Reynes Montpellier
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.

Saturday, April 2, 2016

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) .


OMS TLE-400 lanzafame efavirenz encore1 vih hiv sida WHO Mylan TLE400 Cipla 400 mg
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.

Saturday, March 12, 2016

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.


Stribild Genvoya monotherapy Tivicay Dolutegravir Katlama

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).

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.

Saturday, March 5, 2016

Hypo-Dolu: It works!


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.

HYPO-DOLU Lafeuillade vih HIV cure Dolutegravir Tivicay Hypodolu viral load
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.

Saturday, February 20, 2016

the captain's age


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

the captain's age



It depends on the age ... of the Captain ...

I get asked a question: thus, I answer ...

Perfect alignment of stars! Talk to your doctor about moving rapidly to Tivicay ® + Lamivudine (Ge). Let 6-12 months pass. Then Tivicay ® monotherapy. Let 12 months pass. Then enter the short cycle: 6/7 (6 months), 5/7 (12 months); 4/7 (for life or HypoDolu) with frequent VL, at first.

It depends on what, anyway?


Dr. Weinberg wrote, and justified: the effectiveness of DTG (Tivicay®) does not depend on the dose.
Dr. Sherene Min S has also argued: effectiveness of DTG (Tivicay®) depends on the dose. (Dose-dependent, in English).

Dose-dependent is often understood as in proportion to ... but proportional often means that there is a proportion factor: tricky ... Dose-dependent is the pharmacist's Holy Grail. thousands year old orthodoxy, since we know that a tad of opium is not effective; a bit of opium, you sleep, and too much, then you are in trouble! The dose dependence is a must-have in pharmaceutical development. This is formalized: Phase II trial: escalation of the dose.

clinical trial ING 111521 shows that the number of patients who pass the promising beacon of 400 copies (once there, achieving UD is no problem) are 5/9 (56%) at 2 mg, 5/9 (56 %) at 10 mg, and 9/10 (90%) at 50 mg, in less than 11 days. Weinberg is right: you arrive at the harbor entrance regardless of the dose.

Only, you get faster there with 50 mg. The study was paid for by ViiV ... In addition, it is customary (because of former ARVs) to substitute the speed of the effect to the effect itself. If you had a tumor, you'd be encouraged to see it deflate fast, especially when there racing against time (resistance ...). With Dolutegravir, no resistance, so we don't care, but we can not stop people from earning their salary doing what they were asked to do. This is a mandatory, regulatory study, not a research study.

So, let's assume, for a moment, that the answer is 'in proportion' of the dose ...

Either ... But it is also in proportion to the initial CV.

Paddle EACS 2015 Lamivudine Dolutegravir dose dependant FDA cure Katlama
Paddle EACS 2015 Lamivudine dolutegravir dose dependent FDA cure Katlama

How do we know? Are we really sure?

It is not necessary for the following, to establish irrefutably that this is the case: it is enough to have a reasonable intuition.

In Paddle, almost monotherapy Tivicay®, the results are in the table here. We class the same data in order initials CV, which gives a new table and for those who had not seen the dependence on the initial CV, we decorate the table slanted lines, and there it is obvious .

Paddle EACS 2015 Dolutegravir dose dependant FDA trend vitesse charge virale

One can see: it is convincing! Over the resume is faster undetectable low is obtained. It is clear and confirms what was in trying to attack the ING 111521 monotherapy trial.
In this sense, it is consistent with the HILL equation, where efficiency saturates when all the sites 'target' are inhibited and where to add the inhibitor does nothing more.
Therefore, it is more than legitimate to ask questions seriously dose monotherapy for maintenance of Tivicay®.
This reasonable intuition will allow us to understand how the formulation is overdosed, and how to turn this to our advantage overdose.

For now let us remember that:
The efficiency (here in the sense of lowering speed) is:
- Dose-dependent (in proportion, if you like)
- Depending on the initial conditions (CV ...)

Where we Eff = F (dose, CV, ...) either: Eff. is a function:
- Increasing the dose
- Decreasing the initial CV
And why not...
- The age of the captain ... ;-)

Retain the effectiveness of dolutegravir is not a function of dose; it is up to the problem posed: dosage adjustment is possible!

We will use this in a forthcoming ticket and exploring the Buzz Genvoya®

Buzz Genvoya ®

It's the Buzz! Genvoya® (or its predecessor Stribild ®) could jeopardize the chances of successfully Tivicay® monotherapy, which is the gateway to Hypodolu. To be continued ...

Good weekend and good fuck ...

Saturday, February 13, 2016

CRISPR Heroes


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

CRISPR Heroes

Heroes CRISPR diabolical ... Fables

CRISPR-case.9 is a new publishing method of DNA; it opens up new technical and industrial prospects: read this article World. This is the subject of fashion. And already the subject of controversy. Which can be patented? Who can claim the Nobel Prize?

Any resemblance to the issue in question of Who discovered the virus? Who can patent the corresponding test? The 'Nobels' crush the non-Nobel notoriety? Any resemblance ... Is not coincidental. The story repeats itself ...

We remember that Paris (J. Chirac ...) had dared to stand up to Washington and get a deal.
The time when Paris was audible are gone ...

The squabble explodes in the public space by a historic apology published in CELL by Pr. Eric Lander, excellent teacher and inspirer of great projects, boss of the BROAD Institute, big thing full of money, at Harvard. The free version, complete, is available in my complete bibliographic record, which can be downloaded here. In "General."

The controversy: to simplify, CRISPR is great because:
- This is applicable to humans, therefore Zhang (Harvard) and patents deserves Nobel Price
- It is applicable to all, so Doudna and Charpentier deserve Nobel and patents

Yesterday, European research base. Today patent war between Berkeley and Harvard.
The temptation is to write the story in his own way, and to silence the warning.
It reminds us how to reach a consensus on the Nobel (HIV), it took some deviate. Leibowitch left interesting accounts of that time. The Nobel award more than 3 researchers. And this is not the discovery itself that is honored.
The twenty-first, it's a shame ...
Berkeley replies: with this ticket of Michael Eisen, see this post N. Comfort.
It is true that the maneuvering Lander has dug up the hatchet.
There is something amazing to see an evil genius at the top of his art, and Eric Lander is a diabolical genius at the height of his art.
The recent trial in Lander CELL entitled "The heroes of CRISPR" is his masterpiece, at once so diabolical and yet so brilliant that I find it hard not to stay stunned even if I ' imagine cackling loudly in his den Kendall Square, giant laser weapon in the back, ready to destroy Berkeley him if we do not challenge our patents.

truncated Studies and spin-doctors diabolical

What is important here is the extraordinary ability of the spin-doctors, crowned with sounding titles, to accommodate the sauce that suits them. Even amputate design information.

With us, it is the SMART START and testing, we are rehashed all the sauces. Critics have dared to point out that the excess mortality had not taken place in Europe. Are reduced to silence or marginalize.

In SMART, excess mortality is concentrated in the US (mainly cardiovascular, 92% of deaths for Americans 50% of participants!). In START she appears only in the townships of South Africa, the failing health care system: tuberculosis, suicide, homicide! inconceivable risks with us ....

Geography has a more decisive role that the treatment strategy. But hush!

Transposing among us shamelessly risks that exist elsewhere. Diabolical...

Those who have the means to carry these media battles earn.

Yet our lives are worth more than their profits. Our patients deserve better ...

Sunday, February 7, 2016

Reservoir measurements-1


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

Reservoir measurements-1

Measure your tank: # 1 total DNA-HIV

The draft Backonstage
[...] I am observing seamless, undetectable for 15 months and no further infection with my virologist then we decided to test the mono Tivicay ® ... strong advice of Charles Edward, his arguments did fly ... [...] Beginning February 23 for me and the first record on April 4 and then 1 every month for 3 months, then every 3 months 1 for 6 months and 1 per semester
A Charles-Edouard
I adore you you're really top ... Where are you taking all this knowledge ... THANK admirable

Back, you read me a long time. If I could be useful to you, you see me happy. I wish your project to succeed as much as mine.

How to measure the tank?

Christine Rouzioux we read here (magazine of the French Society of Virology)

The quantification of total DNA-HIV is by far the most used method. It can be applied on red blood cell, PBMC samples (Peripheral Blood Mononuclear Cells) or whole blood. It measures all forms of DNA-HIV present in CD4 + T cells and monocytes, whether integrated or not integrated. This is a global approximation that can be criticized because of variable effectiveness without doubt to extract and amplify the different forms of HIV DNA within the same sample. However, it remains the simplest [...] and usable in many laboratories.

The reference method, it consists roughly to infect a blood bag and see what happens (Viral Outgrowth Essay). In fact, the only method that puts everyone agrees it is to interrupt the frequent monitoring and see when it bounces, in vivo.
The top = measuring time to rebound.
I look 2: measurement of total DNA and HIV-time measurement rebound. I speak here of the total DNA-HIV, now available in lab city. Well ... It wipes the plaster.

Rouzioux total HIV DNA tank Siliciano Hypodolu Salpetriere PCR Viral Outgrowth Essay Already, check your lab does. The CBCV fact they subcontract to the Salpetriere.
Again, this is very recent, it is appropriate to go where we can.

1 It is not therefore not reimbursed codified: So ... Results: within 3-4 weeks
2 it costs only 70 Euros (out of pocket)
Indeed, even when one considers the relief, it has no practical use. The idea that the reduction is done under reservoir condition is false, nothing justifies, and even made Leibowitch proven otherwise. How clinical decision the extent the total DNA-HIV can she drive? In practice no! Unusable, therefore, not reimbursed by health insurance (and that's good and it suits us!)

3 can have its result without going through the doctor box
Genetic analyzes are delivered by hand by the doctor. It's the law ... This is a count, not a DNA analysis: there are blind ... If we refuse to give you the result, ask the service biologist understand and give you your results. Otherwise too bad, wait until the next visit to the doctor.

4 as it is not paid, your doctor can hardly deny you the order.
Indeed, it is useless ... So we do not pay you! But as you pay for and this is more a bottle when your blood test, therefore, safely, on what basis your doctor Could you refuse the order? ... Bingo!

Now you know to do now ... Do it ... Be aware from his own experience that it is possible, simple and useless is a good way to put hysteria tank in perspective.

We have fun with the toys that have been ...

Note of 30.4.2016: I added the interruption by analytical method.

Good Night and Good Bourre!

Saturday, January 30, 2016

Katlama EACS-2015


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

Katlama EACS-2015

Katlama EACS-2015 (Poor Genvoya ® ...)

Read in this lively discussion here:
[...] It would not give me Tivicay ® monotherapy ... so: Tivicay ® + Truvada ®.
600 + 500 euros !!! 1,100 euros / month = this is crazy!
I wanted to try Tivicay ® (+ possibly associated with Lamivudine) but she refused. I hope I do not have issues like in September with Triumeq ®!
What do you think ?
Eviplera ® damn transformed me physically ...

It gives you everything you need to succeed: You do the sorting for some time, you valid (close CV) you let Truvada ® in the closet, you valid (close-CV). Well ... Did she spun monotherapy air to touch it ...

There are only two questions to ask:
1 - Tivicay ® monotherapy (m ') is it possible, and if so?
2 - maintenance, 10 mg is it as good as the 50 mg?

Tickets for EACS-2015 starts here ... Here I pruned the summary of the presentation by Prof. Katlama EACS (Salpetriere, see here) (transparencies are there). This is the perfect example of the study when it is appropriate to read the details: in addition, details are presented. Thank you Christine! If the earlier use of Stribild ® (now Genvoya ®) closes the door of the monotherapy of Tivicay ® 1/4 of these patients, and only to them, they make the mouth!

HYPO-DOLU EACS 2015 monotherapy Tivicay dolutegravir Christine Katlam Genvoya Stribild Barcelona hiv Background: [...]. Dolutegravir, an inhibitor of the latest generation integrase (INI) with high power, long half-life and high genetic barrier in vitro and in clinical studies has potential for monotherapy. Methods: This observational study recruited patients with HIV-RNA CV (VL) <50 cp / ml for at least 12 months, CD4> 350 cells / mm3, with no faults INI; they changed their effective treatment for mono-dolutegravir 50 mg / day. [...]. Data are presented to S24.

Results: 28 patients in total with a median of 624 CD4 / mm3 [...]. Thirteen patients had prior exposure INI (n = 13). DNA median was 195 cp / 106 cells [94-641].

The proportion of patients now VL <50 cp / mL was 96% (95% CI: 79-100) to S4, 100% (85-100) to S8, 93% (76-99) to S12 and 92% ( 75-99) in S24.

Three patients [...] had a rebound with the emergence of resistance mutations INI [...]. The concentrations were in the normal range in all three patients. genotypic resistance retrospective analysis based on DNA-HIV showed no INI-RAM [mutation associated with resistance INI] in patients exposed to Inis pt except for # 1 with 74I previously under suppressive therapy containing elvitegravir .

[...]
The usual Cassandras, journalists photocopying, useful idiots, were too quick to point out the failures 3, indiscriminately. By hiding us the details.

Among the hundreds of patients who tried the monotherapy Tivicay ®, there are only 4 patients where it makes the least (1 in Barcelona, ​​3 in Paris) and in every single case the prior use of the INI first generation ( RAL or EVG) is mentioned as an explanatory factor.

So, I would ask the question:
It is known to contain the risk only patients who used the ancient INI. For others, what about the dose?
This is, among other things, that you propose to explore in future posts.
For us, this study Katlama: it's great! The victory assured!
The results PADDLE (Dr Cahn) and Katlama-EACS2015 open a new field. Stay tuned: our victory is there; our enemies are struggling, unsuccessfully, such fatty fish out of water. Poor ... they entangle themselves ...

Good weekend and good fuck!

Saturday, January 23, 2016

Monotherapy: Olé


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

Monotherapy: Olé


Monotherapy: Olé!
I'd like to go around the world for about 6 months: How to treat? I can not go back to France every month [...] If I understand you started a therapeutic relief to reduce the number of drugs and thus need fewer pills during your stay abroad.

I already told my doctor relief and he will not do it [...]

Otherwise I might be forced to return after three months, it looks like a prison, in short, thank you for your help :)

The only passage in the monotherapy Tivicay ® does not respond to this question: we must learn to reduce the dose: it's healthy and useful.
With conventional treatments: ICCARRE 4/7 or 1/7 (4/7 ICCARRE enough to this project); with the monotherapy Tivicay ®, consider dose reduction or Hypodolu.
Monotherapy Tivicay ® has the wind in its sails. It is understandable...

And for the stock, there is only one way: save, thus reducing the dosage.

There are only two questions to ask:
1 - Tivicay ® monotherapy (m ') is it possible, and if so?
2 - maintenance, 10 mg is it as good as the 50 mg?

Tickets for EACS-2015 starts here ... Here I pruned the summary of the EACS presentation by Univ. Barcelona (transparencies are here):

HYPO-DOLU EACS 2015 Barcelona monotherapy Tivicay dolutegravir Esteban Martinez Barcelona hiv

Dolutegravir Monotherapy in HIV-Infected Patients with Sustained Viral Suppression: A 24-Week Pilot Study, J. Rojas et al.

Goal:

[...] We have tested the feasibility of dolutegravir monotherapy in patients with treatment options limited due to toxicity problems, interactions, or resistance.

Methods:
Patients without failure or without mutations previously documented proven resistance to integrase inhibitors and with plasma HIV-1 RNA <37 copies / mL for at least 12 months had their antiretroviral treatment (ART) changed dolutegravir 50mg OD [ ...]. primary endpoint was the proportion of patients without new treatment failure (do not go through = failure) at 24 weeks.

Results:

33 (22 IP-18 in monotherapy) patients were included [...] 39% with prior AIDS events, 8 (4-13) years with undetectable HIV viral load, CD4 596 (420-843) cells / mm3. [...] Only one patient of 33 had virologic failure at week 4 (88/155 copies / ml). It has been recommended that increasing the dose of dolutegravir 50 mg BID, but he continued 50mg OD. Viral load remained detectable at 24 weeks (79/101 copies / ml). RNA genotypic resistance tests for HIV and DNA at 4 and 24 weeks did not detect any mutation of the integrase. [...].

Conclusion:

Dolutegravir monotherapy is an option that remains to be confirmed in randomized clinical trials.

What remember: it goes smoothly. One exception (of 37 patients): a multi-treated patient coming, especially a treatment with raltegravir (Isentress) this 'failure' with little consequence because the CV is very low: the patient remains under monotherapy Tivicay ® 50 mg / d. Note also that the mutation (118R) is a mutation cul-de-sac that reduces slightly the efficiency of DTG without opening a path to other viral mutations and therefore exhaust.

For us what matters is that it seems to work for 32 of the 33 patients (96%). For one of the two patients who previously took an INI first generation, it does, for the other less ... and when it makes the least, what is proposed? Increase the dose ... The second line following Tivicay ® is Tivicay ®: it is its own antidote.

Question: (? Horse, initial) when it does, what is prohibited to reduce the dose

To repeat: 95% of patients, stable and undetectable, are unnecessary and harmful on-medication!