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

The fourth molecule

By Charles-Edouard!

You can find on the excellent blox of gerard maudrux

Synergies and reinforcement for 1/7 (or even better)

For initiation and continuous treatment, it is historically considered that 3 molecules are sufficient. Practitioners (e.g. Germans) were already doing induction/maintenance. Today too, there seems to be nothing to prevent the use of DTG x 2 /TDF/3TC followed fairly quickly by DTG/TDF/3TC then DTG (1/2) /TDF/3TC or DTG /3TC or even DTG /3TC (in 4/7) as we will soon see. Putting an extra pill, when the circumstance allows or requires it, is admissible...

Videx in addition, a futile intuition/orthodoxy?

The very first successful patient in 1/7 appears in FASEB1, and is described as being on Quad Therapy (NVP/DDI/FTC/TDF). I am not sure if the patient was on this quad before starting ICCARRE or if the boosting occurred along the way. It seems that it was like that, by chance, and that Leibo continued like that considering that the prejuduce (1 Videx more) was not very big with regard to an eventual securing.

He was keen on it, but readily admitted that there was no evidence of the futility (or not) of this reinforcement. To do the right thing (and to please the Stakanovists of the methodology), one would have had to do a good large group randomly allocated with and without reinforcement. Under these circumstances, the futility test is... futile. So not done.

For a long time, I promoted the Leibowitchian orthodoxy of the fourth molecule, aware that there was no formal proof. I have to admit that this did not convince many people. This blog is not a medical advice: you will be inspired by it, it is your choice, you will not be inspired by it, it is also your choice. And if it doesn't work, don't bother to come and bitch about it: this blog is not a medical advice, it's a double-sided cave canem: I don't encourage anyone and, conversely, no one bothers me. Right?

The fourth molecule can be useful: here is why...

For a long time, I thought that we had not done the manipulation that consists in removing the fourth molecule and see what happens. Strictly speaking, as far as I know, this manipulation has not been done. But another one... Which informs us in the same way... Except that we didn't see that it could be interpreted that way.

If the Fourth Molecule had not been removed, it could have been replaced by a placebo. That's what protocolists are like. Leibo was a doctor first and foremost, so the placebo was not his thing... The idea of replacing the Videx with plaster ... I let you judge... Well... However, Videx no longer exists, so it should have been replaced by something, a placebo? no... But...

Replacement of Videx by DTG

As Videx disappears, we start to have a good idea of the 'power' of DTG, hence the simple idea of replacing Videx by DTG. But there, there is a wolf! The literature states that NVP reduces the amount of DTG in plasma. You will be surprised to know that this is a work of Raffi(yes, the same one who... ). If we stick to Raffi's conclusion, it's not a big deal, we pretend nothing happened. Except that Raffi, he looks at 7/7. DTG fills the bathtub, NVP empties it, but since we fill it right after, the bathtub doesn't really get empty. In 1/7, we don't fill the tub a second time! And so... DTG disappears. DTG has an antidote: it is NVP!

We make NVP/DDI/TDF/3TC then we substitute, we think we make NVP/DTG/TDF/3TC, and, in fact we make NVP/DTG/TDF/3TC, i.e., a classical IRT NVP/TDF/3TC... And this? It jumps! Does it always work? No! There are exceptions, but well... We can see that with NVP/TDF/3TC, there is a benefit to supplement with DDI (or something else?)

DTG in 1/7: In TRI or in QUADRI? That is the question

All indications are that DTG counts for two: it is potent (over 4.5 Log) and it has a pharmacodynamic remanence of at least 3-4 d. Of course, we have evidence of success in 1/7...

One way to do suspenders and belt, is to take Morning and Evening. Note that in the free zone, you can find a DTG/TAF/F-3TC combo, at a very low price. In the mafia zone, not yet... Well, it's a bit of a pity... Now, the goal of the maneuver is to catch the payers (social security, etc...) on the Biktarvy ® combo. If the payer gets cheated, that's his business. From our perspective, we do not identify any difference between DTG and BTC(and for good reason!).

In practice, we read testimonials of 2/7 with Biktarvy. Why not? Now, I also don't see what we have to lose by reinforcing a bit... With what? RPV, ATV (without booster, since the usefulness of booster in 1/7 is far from being obvious: futile or even counterproductive, in this context), etc.

Islatravir: addition or substitution?

Especially sinceIslatravir is coming. Well... Overdosing seems to be avoided, on paper(too bad... ). Well... The dilemma of the 4th molecule is there in front of us: Islatravir® is not very powerful (1,5 Log) but very persistent (10 days at least!). It makes you want to use it. As an addition or as a substitution? For me, it will probably be used to replace one of the molecules that I probably have too much of. For those who stayed in IRT all the way down, the question will be interesting. Might as well start thinking about it!

In the news

- A controversy (pro and anti HCQ), a randomized trial and each side claims victory! This is normal: in order to be published, the authors conclude that it doesn't work... This allows them to reveal their data, which show... that it works!

We have a bit the same thing with the Eclipse: all conclude to a quick rebound, because such is the Zeitgeist, but, in reality, it is long enough to be exploited. Nobody would dare to write that!

Genius, but not French...

THE (not THE) French genius, and of its language, is to say THE Covid, as it is quite natural. That's THE genius of the language, it's precisely what can't be reasoned... Especially since in reality we are entering the era of the Covid.E.s...
There is no genius of the Europeans, who taken as a whole, are rather sterile... It is illusory: I could not even name a contemporary Polish or Bulgarian author. And there are other geniuses... Sometimes one remains amazed by other ways, other voices.

Miyasaki appeals to an ecologically sensitive public, so youtube advised me this strange and bewitching video: 450 Subscribers, 2000 readings, we are far from the Raoultian Million views, but still, it's something else... And precisely... It is... different... Enjoy!

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The real insider tip is to know which doctor to go to...