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 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 .

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 ...

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 ...

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!