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Summer 2016: we offered a serial: ANRS-4D and the cheaters
Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - N155H: new scenario (DOMONO) - Nevirapine and Mono-DTG Switch: the Hunchback Trap - calculation error in the primary hypothesis - DOMONO and the benefit for the patients (not for BigPharma ...) |
This was originally published here, in French. We provide this translation for your convenience, practical aspects may differ where you live.
Dolutegravir, R263K and DOLUMONO
By Charles Edouard!
Pr. Philippe EVEN: Each clinical trial is a detective novel, it is first a novel because it is false, and, it takes a detective mind to detect all maneuvers.
At the min. 53:30 of the Even video.
In order to better understand this post, please read again DTG and R263Kand R263K and Darwinian sink
R263K is beneficial, it amplifies the effect of Dolutegravir, and can even explain an Absolutegravir-like effect. This is a beneficial mutation, which is not the stepstone to others.
It is also beneficial to the reservoir (post to come). And it is, at most, commensal of the VL decay. When the pharmacological pressure is lowered, if it is there, well ... As the rats leave the ship, it comes out first ... Even if it quickly becomes invisible, drowned by the fittest virus (the original one).
In the table, a patient is identified with R263K; The authors, by their decision to stop the trial, consider that R263K appears, in a way, say, of a random event, and creates the VL raise: it would be the cause. This is consistent with the idea that the R263K mutant shows resistance to DTG. However, this resistance is very very modest, hardly measurable, and is accompanied by a significant loss of fitness. And also, why does it appear now, after more than a year ?? ...
Ah! They have an explanation: the dose of DTG was lowered by malabsorption: Probably suboptimal gastrointestinal uptake of DTG during 10 days due to gastro-enteritis
Here is our alternative scenario, more credible:
The patient has a gastroenteritis, takes none or little or inefficiently, the medication pressure decreases ... Dosage at 13h is 0.7, ie as my mini-Dolu, so, as expected, the virus takes up, with its commensal R263K, as a signature, not as a cause. Hazard of things, it is seen at this time: what happens if the situation persists: the virus continues its raise, the wild-type (or historical) virus, fitter, overcomes, very quickly, and the R263K fades out, relatively to it: it will become invisible. No visible mutation and a virus on the rise, but not too much... Does it remind you of anything? Look at the table...
In mono-DTG, to optimize the bioavailability, one takes with a meal. As for myself, I also break the pill between the teeth: broken, it disolves better.
Elementary, my dear Watson! Elementary???
There you have it! All ? Absolutely everything ?? All ???
Oh really? The virus goes up with its commensal R263K, along with an accidental drop in drug pressure ... Certainly ... But was it doing there in the first place?!
It is the summer, we take our time: it will be for a next post! It's fun, isn't it?
In the news: DTG + 3TC, in first line, <500.000 and an overwhelming VICTORY
B. Taiwo presented the results, at S24, of ACTG A5353: phase II DTG + 3TC, in first line. It is a little more ambitious than PADDLE (20 patients under 20.000 copies), but less than Lanzafame (20 patients <100.000 copies, in Mono-DTG, with selected patients).
IAS-2017: the consecration of 4/7
Tiring but victorious week: Good Weekend and good fuck
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Summer 2016: we offered a serial: ANRS-4D and the cheaters
Summer 2017: we will debunk DOMONO: - Dolutegravir and R263K - R263K: new scenario (DOMONO) - N155H: new scenario (DOMONO) - Nevirapine and Mono-DTG Switch: the Hunchback Trap - calculation error in the primary hypothesis - DOMONO and the benefit for the patients (not for BigPharma ...) |
This was originally published here, in French. We provide this translation for your convenience, practical aspects may differ where you live.
