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Saturday, January 30, 2016

Katlama EACS-2015


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

Katlama EACS-2015

Katlama EACS-2015 (Poor Genvoya ® ...)

Read in this lively discussion here:
[...] It would not give me Tivicay ® monotherapy ... so: Tivicay ® + Truvada ®.
600 + 500 euros !!! 1,100 euros / month = this is crazy!
I wanted to try Tivicay ® (+ possibly associated with Lamivudine) but she refused. I hope I do not have issues like in September with Triumeq ®!
What do you think ?
Eviplera ® damn transformed me physically ...

It gives you everything you need to succeed: You do the sorting for some time, you valid (close CV) you let Truvada ® in the closet, you valid (close-CV). Well ... Did she spun monotherapy air to touch it ...

There are only two questions to ask:
1 - Tivicay ® monotherapy (m ') is it possible, and if so?
2 - maintenance, 10 mg is it as good as the 50 mg?

Tickets for EACS-2015 starts here ... Here I pruned the summary of the presentation by Prof. Katlama EACS (Salpetriere, see here) (transparencies are there). This is the perfect example of the study when it is appropriate to read the details: in addition, details are presented. Thank you Christine! If the earlier use of Stribild ® (now Genvoya ®) closes the door of the monotherapy of Tivicay ® 1/4 of these patients, and only to them, they make the mouth!

HYPO-DOLU EACS 2015 monotherapy Tivicay dolutegravir Christine Katlam Genvoya Stribild Barcelona hiv Background: [...]. Dolutegravir, an inhibitor of the latest generation integrase (INI) with high power, long half-life and high genetic barrier in vitro and in clinical studies has potential for monotherapy. Methods: This observational study recruited patients with HIV-RNA CV (VL) <50 cp / ml for at least 12 months, CD4> 350 cells / mm3, with no faults INI; they changed their effective treatment for mono-dolutegravir 50 mg / day. [...]. Data are presented to S24.

Results: 28 patients in total with a median of 624 CD4 / mm3 [...]. Thirteen patients had prior exposure INI (n = 13). DNA median was 195 cp / 106 cells [94-641].

The proportion of patients now VL <50 cp / mL was 96% (95% CI: 79-100) to S4, 100% (85-100) to S8, 93% (76-99) to S12 and 92% ( 75-99) in S24.

Three patients [...] had a rebound with the emergence of resistance mutations INI [...]. The concentrations were in the normal range in all three patients. genotypic resistance retrospective analysis based on DNA-HIV showed no INI-RAM [mutation associated with resistance INI] in patients exposed to Inis pt except for # 1 with 74I previously under suppressive therapy containing elvitegravir .

[...]
The usual Cassandras, journalists photocopying, useful idiots, were too quick to point out the failures 3, indiscriminately. By hiding us the details.

Among the hundreds of patients who tried the monotherapy Tivicay ®, there are only 4 patients where it makes the least (1 in Barcelona, ​​3 in Paris) and in every single case the prior use of the INI first generation ( RAL or EVG) is mentioned as an explanatory factor.

So, I would ask the question:
It is known to contain the risk only patients who used the ancient INI. For others, what about the dose?
This is, among other things, that you propose to explore in future posts.
For us, this study Katlama: it's great! The victory assured!
The results PADDLE (Dr Cahn) and Katlama-EACS2015 open a new field. Stay tuned: our victory is there; our enemies are struggling, unsuccessfully, such fatty fish out of water. Poor ... they entangle themselves ...

Good weekend and good fuck!

Saturday, January 23, 2016

Monotherapy: Olé


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

Monotherapy: Olé


Monotherapy: Olé!
I'd like to go around the world for about 6 months: How to treat? I can not go back to France every month [...] If I understand you started a therapeutic relief to reduce the number of drugs and thus need fewer pills during your stay abroad.

I already told my doctor relief and he will not do it [...]

Otherwise I might be forced to return after three months, it looks like a prison, in short, thank you for your help :)

The only passage in the monotherapy Tivicay ® does not respond to this question: we must learn to reduce the dose: it's healthy and useful.
With conventional treatments: ICCARRE 4/7 or 1/7 (4/7 ICCARRE enough to this project); with the monotherapy Tivicay ®, consider dose reduction or Hypodolu.
Monotherapy Tivicay ® has the wind in its sails. It is understandable...

And for the stock, there is only one way: save, thus reducing the dosage.

There are only two questions to ask:
1 - Tivicay ® monotherapy (m ') is it possible, and if so?
2 - maintenance, 10 mg is it as good as the 50 mg?

Tickets for EACS-2015 starts here ... Here I pruned the summary of the EACS presentation by Univ. Barcelona (transparencies are here):

HYPO-DOLU EACS 2015 Barcelona monotherapy Tivicay dolutegravir Esteban Martinez Barcelona hiv

Dolutegravir Monotherapy in HIV-Infected Patients with Sustained Viral Suppression: A 24-Week Pilot Study, J. Rojas et al.

Goal:

[...] We have tested the feasibility of dolutegravir monotherapy in patients with treatment options limited due to toxicity problems, interactions, or resistance.

Methods:
Patients without failure or without mutations previously documented proven resistance to integrase inhibitors and with plasma HIV-1 RNA <37 copies / mL for at least 12 months had their antiretroviral treatment (ART) changed dolutegravir 50mg OD [ ...]. primary endpoint was the proportion of patients without new treatment failure (do not go through = failure) at 24 weeks.

Results:

33 (22 IP-18 in monotherapy) patients were included [...] 39% with prior AIDS events, 8 (4-13) years with undetectable HIV viral load, CD4 596 (420-843) cells / mm3. [...] Only one patient of 33 had virologic failure at week 4 (88/155 copies / ml). It has been recommended that increasing the dose of dolutegravir 50 mg BID, but he continued 50mg OD. Viral load remained detectable at 24 weeks (79/101 copies / ml). RNA genotypic resistance tests for HIV and DNA at 4 and 24 weeks did not detect any mutation of the integrase. [...].

Conclusion:

Dolutegravir monotherapy is an option that remains to be confirmed in randomized clinical trials.

What remember: it goes smoothly. One exception (of 37 patients): a multi-treated patient coming, especially a treatment with raltegravir (Isentress) this 'failure' with little consequence because the CV is very low: the patient remains under monotherapy Tivicay ® 50 mg / d. Note also that the mutation (118R) is a mutation cul-de-sac that reduces slightly the efficiency of DTG without opening a path to other viral mutations and therefore exhaust.

For us what matters is that it seems to work for 32 of the 33 patients (96%). For one of the two patients who previously took an INI first generation, it does, for the other less ... and when it makes the least, what is proposed? Increase the dose ... The second line following Tivicay ® is Tivicay ®: it is its own antidote.

Question: (? Horse, initial) when it does, what is prohibited to reduce the dose

To repeat: 95% of patients, stable and undetectable, are unnecessary and harmful on-medication!

Sunday, January 17, 2016

WHO proves us right


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

WHO proves us right
WHO gives us reason!

It is not allowed to change your mind ... We read with relish this:
There are obvious advantages to treat as soon as possible:
- Avoid the virus develops in large numbers and settled in reservoir cells where treatment can no longer reach
- Be quick undetectable and therefore not contaminating
- Avoid all risks of opportunistic diseases
- Then go quickly to a lighter treatment.

The relief available to earlier treaties, this is factually untrue. Well ... There is progress ... It's hard, but it fits ...

Dose reduction is sometimes presented as an exception, conditioned to a blood test. It is practiced as well in Geneva and Quebec. It is too restrictive.

Dr. Lanzafame (Verona) is the reduction of maintenance dose, without selective condition, other than undetectable achieved and maintained a good time. Dr. Leibowitch same: de facto, its short cycle (5/7 or 4/7) reduced the dose received. Dr. Cal Cohen (FOTO test, total success) even published its concentrations (C Through) well below the concentration 'recommended'. Dr. Lanzafame also published verbatim by patient patient, pharmacological results: undetectable is maintained in all patients including those whose concentration is very low.

The approach went Lanzafame is the universal reduction: it is not conditioned. He tried several maintenance formulas: protease inhibitors, integrase, or non-nukes (Nevirapine, Efavirenz). Total success every time.

Clinicians, poor countries have done the same ... Funding Gates for 12 million USD. This time, in treatment of attack: these are the ENCORE-1 trial, ENCORE-2, EVEN-3. Again, with success.

But what thus takes them all to question the dose imposed by the manufacturer and approved by the FDA? And see, every time, it works!

Try it (must still try ...) it is to adopt.

This is what comes to the WHO, against the current pharmaceutical lobbies, and for the greater good (mental) millions of patients: The valid WHO reducing Efavirenz 600 mg to 400 mg. It is here, p.7.

WHO Lanzafame efavirenz encoure1 hiv hiv AIDS WHO TLE400 Cipla Mylan 400 mg

[WHO] also recommends the use of a dose of Efavirenz 400 mg as an alternative option for first-line for adults and adolescents to enhance the tolerance of efavirenz, following a finding that 400 mg dose was as effective as 600 mg, but with fewer side effects.

The Indian manufacturer Cipla announced this week that it is preparing to launch fixed-dose combinations containing 400 mg of efavirenz. Mylan Laboratories will also launch its own fixed-dose combinations in early 2016 at a price of $ 99 [NdT: year]. UNITAID said that the transition to a 400 mg dose of efavirenz could result in savings of $ 80 to $ 100 million (US) globally by 2020.

The cons, Dr. Gottfried Hirnschall (WHO).

At Mylan, the drug in one pill, once daily taken, bears the name of TLE400. Read the press release.

Manufacturers will apply for approval to the FDA, and get it, why doubt it? It is required to provide the international donors (American ...).

The valid WHO, FDA approved, but you, you are not entitled ... Why?

As effective, with fewer side effects, it's best! Point bar.

Well ... Let us rejoice: The relief came at WHO, without fanfare, but went anyway! When it's in, that's it!

We will discuss the implications for us in a future post.

By then join the discussion. The most active is in Stribild EACS-2015 Hocqueloux

Good Weekend and good fuck!

Monday, January 11, 2016

The brilliant Dr Cahn


This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.

The brilliant Dr Cahn

The genius of Dr. Cahn

Tivicay ® monotherapy, interested. I received the following question:
Under Stribild ® for 2 months on the front line, went to Eviplera ® and Truvada ® + ® Tivicay. Always side effects of Truvada ®, I would experience the mono Tivicay ®.
Why have undergone ® Stribild a priori it could without resistance we exclude from mono Tivicay ®?

I give items on the comment of the ticket: Stribild ®, EACS-2015 Hocqueloux

Questions help me build the note on the presentation of Ch. Katlama at EACS-2015. Thank you! For the impatient, see the slides and abstract.

Given the total blackout in our favorite media, I'm in no hurry ...

The future of therapy under the dolutegravir angle (Tivicay ®) is easy to envisage.

There are only 2 questions to ask, to collectively and individually:
1 - Tivicay ® monotherapy (m ') is it possible, and if so?
2 - maintenance, 10 mg is it as good as the 50 mg?

2 questions, not one more ...

The genius of Dr. Pedro Cahn is to have responded, in part, to these two questions at once.

Its Dual Therapy of attack, without fail, on naive patients, that in the mouth corner. Especially as Lamivudine, hanging keychain with DTG, is very powerful, and do not synergize with DTG.

This almost monotherapy in treatment of attack open, obviously, the door to the results in attack monotherapy (*). It will eventually come out, probably in 2016 ...

Already the US are building their pitch to finance a large trial on maintenance of combination therapy DTG / 3TC. And again at home what is already acquired at home ... The test, ASPIRE (NCT02263326) is announced here, is no different from our test LAMIDOL

PADDLE, too, will be remade in the US: NCT02582684; by the AIDS Clinical Trials Group

The ING-111521 trial has already shown that monotherapy Tivicay in attack on naive patients, it is possible. The clinic will confirm what we already know.
This same ING111521 test which allowed the manufacturer to claim that 50 mg is better than 10 mg. The higher the dose, the greater the response is quick: the speed of response is in proportion to the dose.

True, but we, we do not care: what interests us is the maintenance of the response.
Not the response speed, the attack ... It depends, a bit, of the dose.
Dr. Pedro Cahn shows that it depends mainly on the initial viral load.

Paddle EACS 2015 Lamivudine dolutegravir Dr Pedro Cahn undetectable

I have classified the patients, the picture presented by Dr. Pedro Cahn, by CV before treatment. (See this post)
We see very clearly that undetectable long in coming when the viral load is high.

And also, that entering the home straight, passing under 400 copies, ensuring the ultimate success, is obtained from the 10 th day (look, this is true for 19 patients: 19/20), as in the attack monotherapy trial: ING111521 (9/10)!

With or without lamivudine, the result is the same ... (*)

So, one can bother taking lamivudine (300 mg, 1 time per day) at the beginning. Without losing sight of removing this accessory, futures (*).

The test PADDLE (*) thus sheds light on what ING111521 plans: the maintenance Monotherapy Tivicay ® is possible. (*) = Treatment-naive patients, therefore / or have never taken INI

It also illuminates the second fundamental question: 10 mg instead of 50 mg, is it sufficient for maintenance?

You do not see what PADDLE sheds light on dosage reduction? See you soon for a future post.

It's fascinating, is not it?