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

Wainberg and his lone mouse

By Charles-Edouard!

Our reader Colibri testifies, right on:

The recursive principle makes remission, albeit partial, possible only as an extension of 1/7. And the power of DTG is favorable! Thank you for this testimony !!!

Short of an history of RAL or EVG, no resistance with DTG

The French database has very little resistance data on DTG, and the only known resistances are those that appeared during the Viking trial or similar (in multiple failed patients, including RAL / EVG) and the Katlama trial (EACS 2015, which demonstrated the Achille's Heel).

NO resistance mutation EXCEPT for prior exposure or failure to RAL or EVG. ZeRo, ZeRo, ZeRo. Dixit A. Marcelin (Webcast O332, Glasgow 2016, and PS3 / 1, 16th EAC, 2017):

In France, there has never been evidence of any mutation of resistance to DTG. Except, in patients pre-exposed to RAL or EVG. One will be wary of RAL or EVG which can lead to a reduction of therapeutic options (DTG or Bictegravir).

To claim that Mono-DTG does not work, with no consideration for the Achille's Heel, is an imbecility of the first order. More stupid than that, i have never seen: Dr. Marta BUZZI (abstr. PS1 / 2) pools the wool everyone's eyes, throws the baby out with the bath water, writes a stupid 'meta-analysis' that mixes patients with Achille's heel (high risk) and patients unaffected, which, of course, falsify the outcome. And I spare you all the idiots who echo it!

Mono-DTG in the humanized mouse

Mark Wainberg was the ardent ambassador of a miraculous DTG that was free of resistance. His prediction, already old, prior to the trials, was, for short, that Mono-DTG would work well on naive patients, rather well in the preexposed patient, and not too much in the patients with prior failure (in particular, failure to RAL or EVG).

To validate this prediction, one would need some clinicians to get to it.

Big Pharma sponsored clinicians? Do not count on them! The choice is thus very limited ... There are no many candidates... So, our good Dr Wainberg undertakes to convince the clinic that it would be interesting to try Mono-DTG on naive patients and will mount an experiment with an animal model: the humanized mouse. It is lesser than primates and also cheaper.

The green mouse: a pre-scientific fable

An old French, strange, Nursery rhyme that dates back from a pre-Darwinian era (see : Mary Had a Little Lamb). Read on Wikipedia or see the video:

A green mouse
Who ran in the grass
I catch her by the tail,
I show her to these gentlemen
These gentlemen tell me:
Dip her in oil,
Dip her in water,
She will become a snail, all hot.

A hastily conclusion

If we limit ourselves to the conclusion, here, we read: We show that Dolutegravir as monotherapy is not sufficient to maintain the suppression of HIV and that resistance mutations differ from those reported in tissue culture experiments.

Holy Shit, here we are in despair!

A closer look (which nobody ever takes...) shows that among the 5 mice, treated in Mono-DTG, only one fails. Let's look closer:

The mice have very high initial VLs (> 100,000): they are small animals. The effectiveness of mono-DTG, depends on the dose AND the initial viral load. However, the dose for the mouse is calculated according to a heuristic formula. In general they divide by 12, here they divided by 70 ... We can therefore fear that the dose is, all things being equal, a little low. In fact, serum levels are similar to what is found in humans. It is observed that the serum dose of the mouse that fails is 50% lower than the others ...

The mouse that crushes our Mono-DTG dreams has two adverse and combined characteristics: high VL and low DTG dose.

Fortunately, Lanzafame saves the day

Mixing high-risk patients and others is mediocre medicine.

In contrast to Dr. Buzzi who, shamelessly, mixed patients at risk (Achille's heel) with patients without risk, Dr. Lanzafame works in the favorable quadran: moderate VL (<100,000) and standard dose.

Wainberg validated	Wainberg's Forecast	Clinical results	Clinical trial	Forecast Quality
patients with failure	so-so	so-so	Viking
Maintenance 1	rather good	rather good	BMM+P
Maintenance 2	good	good	BMM+P (except. AH)
naïve patients	Good	Good	Lanzafame

Like everyone else, he understands Wainberg's prediction, and embarks on Mono-DTG starting with the most favorable patients: those with low VL. Dr. Pedro Cahn did the same with his patients whose VL was <20,000 under DTG / 3TC.

In the news

- FDA authorizes a compliance snitch. Treatment obligation is getting closer!

- Excessive indication extension: At 130 you are in hypertension! Americans are morons!

- Innovative proposal by N. Chomont: target the reservoir right at primo-infection. Lots of trouble whereas we have a simpler and more effective method: Cycling (we will get back to it...)

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Have a good Week, good fuck and do not abuse of meds/drugs