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 #1
By Charles-Edouard!From an astute reader:
The discussion on DTG 25mg will be interesting, and, super important with the announced arrival of the injectables, where you will be able to take half a dose, without risk of forgetting...
DTG 25mg: it's time to open the debate!
Science is the approach that keeps us from getting it wrong. (inspired by Carl Sagan) Science is the honest search for knowledge about reality (PZ Myers)
It is the art of asking questions, good questions. Let's open the debate on an inspiring, edifying, exciting and life-saving subject. The doctor has the privilege of prescribing: choice of molecules, dose and rhythm. This privilege has been distorted by not using it. It has become unbearable and will become even more so: the combos are constructed at the sole whim of the industrial and financial Lego, the doses chosen in spite of common sense, and the rhythm, without even taking into account the chrono-physiology of the virus.
While the overmedication is obvious, since the arrival of Tivicay ®, nobody asks the question: but why the hell so many milligrams: 50! only that!!! There is no justification for such a choice. However, the drop-out rate, due to side effects, is 10 to 15% after 3 years, while on the other hand the antiviral power is unequalled, and purely virological failures are rare...
When one is so close to the ZeRo-failure, one can legitimately ask oneself the question: have we not put ourselves too far from the cliff...
We open the debate with this simple question: where do you get the idea that 50 mg are necessary? (in general, and for me, a patient, in particular)
One of our allies laughed at his colleagues who poison their patients with DTG triple therapy, while he does bi and mono. To which I replied that he was just as much at fault for never having asked himself the why and how of this 50 mg...
Here is how we will explain the question:
- 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
- DTG exists in 4 doses
- DTG-25 mg has been evaluated and we don't tell you about it...
The abuse is so blatant to our readers that the feeling of a plot against us and our finances overwhelms them. Let's stick to the facts:
The original pharmaceutical sin: the slant and the S
The pharmaceutical grail: the S curve. Galen is credited with formalizing the following observation: the slave prepares opium for his master, who is insomniac. Too little, it has no effect, the right dose, he sleeps well, too much, it kills him. Over a certain range, the effect is in proportion. 2 times more and the effect is doubled. Hence the idea of an oblique line, with, at its foot, a gentle slope, and, towards its highest point, either a saturation (it is then a medicine) or an explosion (it is then a poison). It is basic and primitive, of course, but that is how it works, in general. From the name of Galen, we call the art of preparation: galenics...
The Grail for the pharmaceutical industry is to find this S-curve: once they have the curve, they are almost sure to succeed, especially in terms of regulatory approval: it is so canonical that their presentation to the authorities will go smoothly. Of course, after the first obstacle: toxicity.
In the Dolutegravir story, you may have missed an episode: ViiV (GSK) had, initially, a very different plan ... The basic idea was to put on the market a lambda INI, like Raltegravir or Elvitegravir. But it was too toxic. That's why ViiV is in trouble... Nothing but old molecules in the portfolio and nothing to renew.
Another company, unknown to ARVs, but known elsewhere(we'll come back to this), Shionogi, Osaka, Japan, has a 2nd generation INI, a good candidate. Shionogi: Kadors of inhibition! ViiV buys the rights for 10% of its shares (estimate: 2 billion dollars, anyway...) and royalties (unknown percentage, probably high). Who from Renault or Nissan has the power? In practice? Here, it's a bit the same... ViiV is rather the false nose of Shionogi. The introduction of Dolutegravir must be successful at all costs, the survival of ViiV depends on it.
The S-shaped efficacy curve means that beyond the linear zone, when the dose is doubled, the effect is not doubled. But, it costs twice as much... You have a little hunger: you eat a small banana, it does it... But well... Just... So you eat a second small banana, just to be safe. We all get trapped... Eating a small banana was a great plan. The second one is an extra soul, the angel's share. For a very marginal benefit, it cost you twice as much.
The cost increases linearly, in proportion; the desired effect saturates.
the escalation test is mandatory but they don't care
Once the phase I test (toxicity) is over, the regulations require a phase II test: dose escalation. In practice, the dose that will be retained is part of the tested doses. If there is no additional benefit to increasing the dose, there is no need to increase the dose.
The FDA, which was historically established to protect the patient, imposes this formalism. However, in view of the results, it is not the FDA that decides on the dose... The industry proposes, the FDA disposes. So the FDA does not formally impose the optimal dose.
The manufacturer can choose to market one or more doses. Faced with several possible dosages, the manufacturer(we specify the manufacturer) makes choices, choices that he will optimize in order to maximize his financial income. In principle, he will be cleared of these choices by the presence of two recourses: the FDA (or the ANSM) can refuse, and, in fine, the physician can adjust the dose. The FDA sets the rules of the game in advance: the document is here...
The industrial pharmacist only proposes... The responsibility of the dosage is medical, not pharmaceutical. In practice, the only last line of defense against poisoning by cumulative toxicity is the patient herself.... So the escalation test is only a formal exercise, whose conclusions the manufacturer can easily, under some excuse, ignore.
EFV 600 mg an unfortunate precedent
The phase 2 trial clearly indicated an advantage to the 200 mg dose. There was no objective reason to choose 600 mg. Apparently no one can say who chose 600 mg, under what circumstances, and on what authority. Every time you brought it up, you were sent back to your 22m. Until the ENCORE-1 trial, its validation by the WHO, and the marketing of the product, which nobody, nobody talks to you about! They are all walled up in a complicit silence... With DTG, it's the same thing again, but we know the actors and their role... How much is EFV overdosed? 2 times? 3 times? 6 times? Who knows... With DTG, we go to frightening multiples: 2 times, 5 times, 15 times, 25 times ... Amazing!
Well, let's continue next time...
In the news
- HIV infection is no longer decreasing in France. Repeating the same mistakes leads to the same failures. Targeted screening has reached its limits... Adding another layer will only have a marginal effect.
- Colorectal cancer screening is so boring that it is being abandoned. We are sorry in advance about the 'sales' of the reimbursed condom. A good intention, ridiculed by the administration...
- We learn, thanks to an Actupian document, enlightening and staggering at the same time, that Gardasil, this unfortunate vaccine so expensive and so controversial is now free in CEGIDD. If you are at risk (e.g. young gay man), this is to be considered carefully. The benefit/risk ratio is crap for the general population (girls and/or boys, who cares), but for a person at proven risk, it's another matter.
For my part, being at high risk for Hepatitis B, I am vaccinated. Not to the point of demanding, loudly and clearly, the vaccination of infants! Forcing a medical intervention for the sole benefit of others is a crime against humanity (Nuremberg jurisprudence)
- One learns, by the way, a decision taken in secret: the BCG vaccine, whoseinefficiency will have been demonstrated only later, is no longer compulsory for the health workers. The scandal is so huge that we wanted to get out of it by the back door, touch by touch.
Today the BCG is buried! But they are not going to trumpet it from the rooftops. Some vaccines are useful, others not! You have to stop talking bullshit... Forcing people to take useless or even dangerous vaccines is putting gas on the fire and feeding the anti-vaxers.
overmedication is an opportunity if you know how to use it!
