This was originally published here, in French (link).
We provide this translation for your convenience. Practical aspects may differ where you live.
DTG-25 mg episode 3
By Charles-Edouard!In margin of the Lambert Affair (out of our subject, here), a letter of Dr S. PALIARD-FRANCO:
Oh, come on!!! Science and Faith are not in harmony. It is a misplaced trust to place it in those who privilege conviction over proof. Joyeux is a religious activist, almost homophobic... Here is a doctor, writing, in her capacity, to another, Minister of Health, who affirms, right in the eyes (as Dr. Cahuzac would say): by his will, he could have contracted a fatal infection. A deficiency in cellular immunity on demand!!! The proof of his will would be that his immunity, autonomous, insubordinate, works... And, in addition, one could even choose the infectious agent for oneself... One can commit suicide at the first pneumococcus passing by. It is the other side of the same joke that would like the force of conviction to heal, miraculously, a Lourdes in reverse, so to speak.
Many people place their trust in soul supplements (homeopathy, prayer, yoga, overdosing, overprescription...) that viruses, bacteria and macrophages have no use for. We must denounce it. No! criticizing an idea for being false is not a discrimination. Mocking an 'invert' (cf Joyeux), is! To affirm that the Faith of some does not cause harm to others is inaccurate. Misplaced conviction rots everything around it.
Let's go back to our sheep, with our minds cleared of this parasitic nonsense...
DTG-25 mg episode 3: DTG-50 mg, criminal chemical incarceration
This is also a scam of a somewhat original kind. As in prestidigitation, the trick is to divert attention from what is actually happening. The context dazzles us, collectively, and we get distracted, including by the question of Mono or Bi therapy, while the trick, the deception, is right there in front of us.
Their novel is an affabulation for the enlightened. They have committed their crime, before our astonished eyes, and have even signed it: the culprits have named themselves as if to better conceal their cheating.
We had already drawn up the picture:
- the original pharmaceutical sin: the slant and the S
- the escalation test is mandatory but they don't care
- EFV 600 mg an unfortunate precedent
- the trauma of multi-dose rosuvastatin
- DTG and the famous specifications
Our investigation continues...
The curse of efficiency lost but not quite
During pre-clinical development, they will realize something that will satisfy them while posing an unexpected problem. DTG is remarkably well designed... In the laboratory, after many attempts, one always ends up selecting mutants; one cannot think of biology without Evolution. The mutant loses fitness, of course, but gains resistance. It gains more or less resistance. If it gains a little, it remains susceptible to about the same dose; if it gains a lot, the molecule loses its effect, almost completely: the dose must be multiplied to overcome it; this multiplier coefficient, FC for Fold Change, is the indicator of this loss of effectiveness. It is quite well known: the mutation at position 184 confers a resistance to Lamivudine with a moderate FC (ca 3.5): it remains usable. Q148K gives a FC of 83 against RAL and 1700 against EVG: here one should not dream anymore, one would have to multiply the dose to stratospheric levels to overcome it.
Under DTG, and in patients naive to INIs, it is almost impossible to develop mutants with moderate or high FC. Seki explains here:
All single mutants [...] do not alter [DTG] activity by more than a factor of 5.
Fujiwara completes here, I quote:
On the other hand, if you already have a mutant, typically acquired under RAL or EVG, acquired by you (a failure for example), or by whoever gave it to you, this mutant can mutate again and have a moderately high FC, high but not prohibitive: FC between 10 and 20. That's a lot and not too much at the same time. It would have been better if this FC had been a bit lower, but 20 is playable! Hooray! We will be able to bring a solution to the patients of group 2, those who are up to their necks in shit. And at the cost of a higher dose. The FDA will give you anaccelerated MA, which will allow you to exploit the patent for another 2-3 years .
So for group 1, you're going to need a dose for HR < 5, and for group 2, you're going to need a dose for HR between 25 and 50.
A dose for group 1 and a dose for group 2: and these are not conspiracy theories: there is indeed a dose for group 1 patients and another for group 2 patients: this is written in the instructions in the box!
One dosage for some (the vast majority), and one dosage for a few others, perfectly identifiable.
The problem jumps out at you: the requirement is a ratio of 1 to 10, but the suggested dosage is in a ratio of 1 to 2. Can you see the trick? The CF is low for group 1 and ten times higher for group 2, with the icing on the cake that you can't switch from group 1 to group 2. 2 needs, 2 dosages, but the ratio of needs and the ratios of supply differ by a factor of 10!
And the whole aberration comes from there! If your cab chooses a slightly longer route, it passes... If it goes around the ring road 10 times, it's a real swindle. Well, it's the same! At 50 mg, you (from group 1) are swollen by a factor of 10!
The curse of lost-but-not-quite-effectiveness could have been a problem for ViiV, but they're going to pass the buck, and the curse is now on you. We'll see next time how ViiV will succeed in his trick, no one knows...
Towards the obligation of treatment / Judiciarization
David Hynd must attend daily appointments if his HIV levels exceed a certain threshold. Read here. This is the first time that British Columbia has use the courts to force someone to take a treatment against HIV. Let's bet it's not the last... What's up? We didn't tell you about it?
In the news
- DOVATO (DTG/3TC Combo) is announced! What??? The Gilead-o-latre media is not telling you about it ???? Of course, there will always be some idiots who will entertain doubts and lead the poor patient into a daily and deleterious TRI. And others to believe that it will be cheaper. 27,540/year Still!. It's too expensive for Lamivudine ($6600/year for a generic sold for $30/year to NGOs and $300 in India) and 50mg of DTG, which is far too overdosed! Our discussion on DTG-25 mg is very timely!
- Atripla® in 1/2 dose works as well as in daily dose: We already knew that! We have the confirmation here: Randomized clinical trial of the efficacy of every other day fixed-dose efavirenz/tenofovir/emtricitabine versus continuous therapy. When is regulatory listing expected? Morlat, are you there? Morlat, do you hear?
- Hurray!!! Finally a study that shows that the Eclipse is manipulable: We demonstrate a reduction of the reservoir by measuring what, only, we care about: the Eclipse. The new Gilead's 'shock and kill' clears deadly virus in monkeys. As usual, the natural Eclipse is, in median, 21 days.
The French genius
What is this cool music you are listening to right now? Oh, in its reference version by the lovely Scott Ross, it's a bit abrupt; KEMPFF makes it subtle, audible, invites us to to bird recallby J.Ph. Rameau, otherwise a bit old-fashioned. If you liked KEMPFF, you might like his Bach Sicilienne BWV1031
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overmedication is an opportunity if you know how to use it!
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