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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.



tank and intermittence

By Charles-Edouard!

Intermittency, especially dynamic remission, is the repeated exploitation of a documented observation: the HIV Eclipse. The origin of the intrinsic difficulty that HIV has in resurfacing lies in several factors. One theory related to the extended exploitation of the Eclipse is the Choke-and-Mute(which I formally initiated). The Eclipse is observable, but few people are aware of the extraordinary opportunity it presents. A vast majority of physicians are unaware of its existence. Any discussion of intermittency must begin with a reminder of the Eclipse, and I will return to it in a future post.

Cellular DNA and Reservoir: an incongruous measure

A recent article (High' antiretroviral deintensification strategy and cellular HIV DNA levels) brings a recurring issue back into the spotlight. Modest (here EFV or NVP at 200 mg + 3TC, in 7/7) and effective disintentisation (RNA maintained at < 20 cp) would have no effect on HIV DNA (reservoir...). The Rouziouist hysteria would like to pass off the (pseudo) measurement of HIV DNA as quantitatively predictive of something.

It doesn't matter that it is a very bad predictor! A first scam was to make people believe thatHIV DNA is a predictor of the progression to the disease state (in this article). The measurement method, under active replication, shows at most that DNA (without treatment) and RNA (without treatment) are correlated. Big deal!

Especially since, in this case, what matters to us is the DNA under the undetectable cloak. We don't care about what happens outside the treatment.

A tendentious argument would be that lightening in general, or intermittence would increase the reservoir... So what? What is the interest of a low tank, if not a possible disposition to the long eclipse. Contemplating, as some do, its low DNA, saying that taking bigotry his treatment in 7/7 preserves this low reservoir, without being able to explain the advantage of a low reservoir (under treatment) is pure intellectual masturbation.

To help you out on the subject, I remind you that CHUN, in Toronto, took 2 patients with ultra-low reservoirs (in the Rouziouist sense) and made an interruption: one lasted 3-4 months, but the other... 1 week... Post-treatment controllers exist... But we can't predict who will be and for how long... DNA measurement is not a predictor of post-interruption control

Reservoir and persistence

There is no problem in HIV that cannot be solved. No problem... The treatment is effective, devilishly effective.
You deplore the fact that some people are diagnosed too late? Make the screening generalized and mandatory: technically it is possible.
Are you afraid of transmitting the disease to your partner or offspring? Take an effective treatment!
Multi-resistant virus? Today's treatment options include solutions for everyone.
Side effects? With intermittence, you have to be kidding!
The only real technical problem is the existence of a reservoir that serves as a trigger for a resurgence of the virus.

That's the only problem I have. If you have other problems, they are yours, not mine. Being the victim of an isolated incident does not make me a necessary prevention or alleviation/intermittence enthusiast.

The Rouzouist theory of an immediate rebound is false. The Silicon theory of an unquenchable reservoir for all is probably wrong too. With Super-Intermittence, the problem does not change in nature (I have experienced the failure without prejudicethe tank is not extinguished), it changes degree.

Tank, averages and trends

Siliciano(source here), ANRS-4D, etc. all make the same mistake. There is no conceptualization of what is happening in terms of readiness to rebound, by dint of attacking the other side of the Eclipse, where it closes. I went to Pasteur to plead for it: in vain... I presented the choke-and-mute there, which is a sketch. But, beyond this meritorious effort, no progress was made. And we didn't move forward because I didn't publish more, since I'm the only one who explained the importance of this question.

The mistake made by Siliciano, ANRS-4D, and so many others is to compare the mean (and standard deviation) between a before and after, over one year. This is the same mistake as for Levothyrox. Knowing thaton average DNA goes down too slowly (Siliciano) or does not go up (ANRS-4D...) has only one merit: that of not grossly invalidating the chosen dosage: From the point of view of the reservoir (DNA), the lifelong horse treatment (Siliciano), the modest lightening (ANRS, etc.) are not invalidated... Big deal: who cares, really... What matters is whether there are discrepancies. If some people start high and end up low, while others do the opposite, on average it is stable. What would be interesting to know is if there are people who diverge: either their 'true' tank goes up, or the 'true' tank goes down.

The convincing method is both the measurement tool and the intervention; the intervention is the exploration of the eclipse from below (successively going from x/7 to x/14, x/21, etc.); the measurement is to stop and look at 7,14,21, etc. Whether one pushes the exploration to the extreme or makes the measurement of the Eclipse it is the same thing. I went into extreme exploration mode, not to get rid of a toxicity, but to measure the Eclipse.

What interests us are the trajectories, over 2, 3, 4, 5 years. I make my trajectory, with the Rouzioux method... Well... I can see that this is not very interesting. Even 6 months after a dazzling RNA rise, I was already back to 1/7, and the reservoir (DNA) remained in its handkerchief: it is there, but measuring it regularly did not bring me anything. I continue nevertheless.

Reservoir and Strategies

At Pasteur, I presented a comparison between the Siliciano approach, the Wainberg approach and the Leibowitch approach. It is S. vs W. vs L. . Ergotate all you want, the only one that is accessible to you is the L. You don't have the tools for the S. nor for the W., but that's you... I'm the one who made the comparison, I'm in a good position to judge. And I can't prejudge what works on its own: I tried S. and L. and W., successively, in that order. For me, S then L then W did not lead to a disappearance of the tank(objective: the Infinite Eclipse). This time I try S + W + L. It's cheese AND dessert.

In the meantime, I have lost all attraction for the Infinite Eclipse... At 1/15 (or even 1/21, 1/30), I no longer see the point of going for the post-processing control. Bringing my release day from January 26 to 12 and then to 6 is a lot of effort for a very small gain. I'll gladly wait for Islatravir to bring the issue back up.

The fact remains that the 'true' tank can go in 3 directions: up, steady or down. If the hypothesis that the time to rebound is proportional to the 'true' tank is correct, then the rise of the tank should shorten the Eclipse to the point of dropping those who have been in super-intermittence for a long time. However, this is not observed.Rothenberger's study does seem to show a negative (and significant) relationship between Eclipse and time spent off treatment. If this were true, it would keep veterans and those treated too late from a near remission (1/15, 1/21...), but not the others. However, the (too?)-early treated are, in proportion, more and more numerous. The (too?)early treatment is to the detriment of the patients, except for those who have understood that the introduction of super intermittence in their strategy reverses this detriment favorably.

In a very next post we will go hunting for the predictive factors of the Eclipse!

Integration, tank, eclipse, drowning: same fight!

Integration, reservoir, eclipse, drowning are facets of the same specificity. In our context, the article Pro-Bono of Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications. (Avettand-Fènoël , Rouzioux & al.) and stop believing in everything and anything.

Is it even possible that the DNA goes up while the RNA does not? Show me a single case where you have a DNA rise in a context of no RNA rise. Only one case... So try to invalidate the assertion I am making here: Under RNA kept undetectable, DNA never goes up. Never!

Answer this obvious observation: there is an obvious and repeatedly demonstrated Eclipse of HIV, while there is no Eclipse of HBV. However, these are the same drugs (TDF/F-3TC), and therefore the same pharmacokinetics... S+/HBV+ are excluded from Quatuor (ask yourself why?) while S+/HBV- pass with flying colors and are candidates for OMNIBVS?

So go take a look at what integration is all about.

That the constitution of the reservoir is very early in the infection is generally accepted... This is what archives the founding virus and makes possible its ultra-majority resurgence, without treatment, that is, for all practical purposes, the therapeutically relevant disappearance of the acquired mutants, i.e. Drowning. Of course, it is necessary to give it time (therefore to have it) as it is attested in the publication FASEB-2.

Weekly intake and 1/15

Sunday the 26th will be my Liberation day!
Note: I just published my catch chart.

In the news

- ViiV has been rejected by the FDA for its injectable. Officially for a technicality see here. Well... it's only a postponement, and maybe a good plan for ViiV which could ask for an extension of its patent. Nevertheless, the usual parrots have kept you uninformed, that is to say trained, formatted, as agreed in the specifications.

- The pearl of the moment:(in Le Figaro): Denis Moreau: 'It is not because I am a believer that I am a fool!'. Well yes, precisely... To think is to give oneself the freedom to change one's mind, to believe is the opposite.

- Where do we find data on the Eclipse? In the trials on vaccines! For example. NCT02767193. Well... I'll read this and we'll see what we can learn from it...

Have a good weekend, good stuffing and not too many meds... Right?