Possible cure? not yet ... But years of remission: some 405 (and soon 1045) patients included in Short Cycle trials show that we can go from daily HAART (HIV) , gradually, to less and keep the virus undetectable with a single weekly dosing. Patented ICCARRE, now recommanded by French Guidelines, and HYPO-DOLU: Why? For whom? How? It's explained here...
In maintenance, one can question the relevance of a daily Truvada®; with the arrival of Mylan's Truvada ® generic, and soon of Atripla ®, you can discuss the daily half-pill.
Here comes the Great Single Capsule !!!
The trick: the Triple Zero 000 capsule
Just type "Triple Zero Capsule" or "empty capsules 000" in Amazon. Direct link. Or ask your pharmacist. The capsule dissolves immediately and completely in the stomach.
Here with 2 x Tivicay® + Lamivudine. It also works with 1 x Tenvir or Viread® (TDF) and probably generic Truvada®.
I am at 2 x 50 mg DTG + 300 mg 3TC, 1/7; With the fall, I caught something, and the 3-month VL raised just above 50. Not enough to scare me: I play safe: 15j. in 7/7, then 15j. with single capsule 3 x 50 mg DTG (Wednesday and Saturday). Then I will carry on with a single capsule 3 x 50 mg DTG, in 1/7, Saturday, with meal, and VL 1 month later.
A 100 capsules pack (2 years, taken weekly) will cost you $ 10 (including shipping); a 1000 pack (3 years in 7/7): $ 30; So between $ 1.5 and $ 10 a year!
Generic of Truvada® = the end of Triumeq® ?
As the generic of Truvada® (Mylan) is 179 euros, instead of 406 euros, this combo TenofovirDF / emtricitabine (Ge) + Tivicay® (dolutegravir) is at 788 euros instead of Triumeq® (ABC / 3TC / DTG ) at 928: one saves 140 Euros per month and avoids the calamitous Abacavir. 1600 Eu Less / year!
Tivicay® + Truvada® was the most expensive: this is no longer true, thanks to the generic, and with the 000, we regain the comfort of a single capsule.
Generic, ric, ric, ric
The inside diameter of 000 fits exactly that of Tivicay®, and then, you complete; Done with opening several boxes, or asking oneself "Did I forgot X or Y": for $ 5 you can enjoy again the comfort so much praised by BigPharma and their collaborators!
The ICCARRIAN veterans are still dreaming of an all-in-one Quadritherapy: For us, it's solved! Is this trick of interest to you? Thanks for sharing your experience!
Have a good Week, good fuck and do not abuse of meds/drugs
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.
- 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...)
Most HIV-positive people in France take daily treatment for life. But the possibility of easing this constraint is looming for patients on triple therapy, i.e. more than 100,000 people (France). A major trial began in September 2017 [translator's Note: English here] to confirm, in the continuation of a smaller trial, that patients can skip several [Note: consecutive] days of treatment in the week without risk to their health.
In France, some 300 patients have already switched to a "intermittent short-cycle" treatment method. For years, they have taken their medication four [Note: consecutive] days a week, instead of the seven days as per official protocol. And they are doing well.
The new trial, named Quatuor, was launched by ANRS, the French Agency for Research on HIV / AIDS and Viral Hepatitis. It aims to show that there is a benefit for the patient to take his triple therapy only four days out of seven, compared to seven days out of seven. 640 volunteers are being recruited [translator's Note: English here] in the 65 public hospitals involved in France, including the Caribbean. Dr. Pierre de Truchis, infectiologist at Raymond Poincaré Hospital in Garches (Hauts-de-Seine), is the principal investigator of this trial.
It can be assumed, however, that physicians will not wait for the results of this study to suggest to some of their patients remove three days of medication per week. The prescribing recommendations published in May 2017 [translator's Note: English here] for the medical care of people living with HIV, under the aegis of the National AIDS and Hepatitis Council (CNS) and the ANRS, go in this direction. "On a case-by-case basis, under conditions similar to those of the studies carried out, a strategy of intermittent take four or five days out of seven can be considered," say - cautiously - the experts. It should be emphasized that such a change implies a rigorous medical follow-up, with close biological examinations.
Fifteen years in favor of treatment four days a week
There is now a 15-year expertize in the safety of intermittent aleviated maintenance therapy. The main experiment is conducted since 2003 as part of a protocol called ICCARRE, an acronym for "intermittent in short cycles, anti-retroviral remain effective". This program was initiated by Dr. Jacques Leibowitch, a known figure in the fight against HIV / AIDS. He was the instigator, in France, of tritherapy which, in 1996, transformed a mortal pathology into a chronic affection.
Patients followed by Dr. Leibowitch and his colleagues at the Raymond Poincaré Hospital have thus gone from seven to five days of treatment a week, then to four. In spite of this, their viral load remained below the detection level. These results for 48 patients were considered sufficiently robust by the international scientific community to be published in 2010 in the Faseb Journal. The same experiment led to a second publication in 2015, with a greater number of patients (94, precisely) and more years of hindsight.
That year, the direction of Assistance Publique-Hôpitaux de Paris (AP-HP) and Versailles Saint-Quentin University, the two employers of Dr. Leibowitch, jointly invested in the filing of two international patents , one for so-called "maintenance" tritherapies at four days a week and less [translator's Note: English Patent_US20120283177], and the other for the use of innovative quadruple therapies for this purpose[translator's Note: English patent_US20120270828].
A first clinical trial nationwide
Convinced by the first results of the Iccarre protocol, ANRS launched in 2014 a two-year clinical trial conducted in 17 centers in France, named 4D (English, four days). The doctors received many applications to participate in this trial, to the point that they had to refuse, as entrusted to me by Professor Christian Perronne, the principal investigator. The findings were presented at the 2016 International AIDS Conference in Durban, South Africa [translator's Note: English poster]. They indicate that 96 of the 100 patients in the trial who followed the dosing regimen with four consecutive days out of seven did so successfully. 3 patients had a new detectable viral load by the fourth week of the study. It has become undetectable again, with the return to a daily treatment regimen. 1 patient left the study.
The results encouraged the ANRS to continue in this direction with the Quatuor trial. The new study has, this time, a "control" group consisting of patients who will continue to take their treatment seven days out of seven for 48 weeks, to allow for a comparison. This methodology meets the requirements of health authorities for the level of evidence to be provided before a change in their prescribing recommendations.
"Quartuor seeks to demonstrate that the four-day-seven strategy is non-inferior to the seven-day-seven strategy, in other words that at equal effectiveness, patients in the Aleviation group will get secondary benefits from this protocol. 'side effects, better compliance ...)', said the ANRS on September 1 on its website.
Daily treatment, sometimes badly perceived
In fact, the stress of taking a daily treatment can be a bad experience. Many patients are less regular in their dosings after several years of treatment - a problem for many chronic diseases. It is very risky for patients to reduce their own treatment without medical supervision. [Translator's Note: this is a statement which we oppose]
In addition, the use of anti-retroviral drugs is sometimes accompanied by side effects such as nausea and diarrhea, as well as fatigue. Dosing reduction can be accompanied by a reduction in these effects.
What will happen now? It is only after the results of the Quatuor trial, at the earliest in 2019, that the practice of four days out of seven can officially be recommended in France. [Translator's Note: it is, in fact, already recommanded - Morlat 2016 - at time of this translation] Abroad, it has not drawn much interest. Not even in the United States, the country that initiated first, in 2001, a path to Short Cycle that Dr. Jacques Leibowitch had followed.
It is surprising that this reduction in treatment is still, more than fifteen years later, at the experimental stage.
It must be said that in France, the historical patients associations in HIV / AIDS have not grasped this issue. They focused on other priorities such as preventive treatments, pre-exposure prophylaxis (PreP). On the other hand, patients of Dr. Leibowitch following a lighter treatment created an association, The Friends of Iccarre, under the impetus of artist Richard Cross. It aims to promote intermittent therapeutic aleviation for all [translator's Note: English abstract].
The doctor free to prescribe according to the code of medical ethics
Only a few AIDS clinicians in France have begun to aleviate their prescriptions. Article 8 of the code of medical ethics allows them: "Within the limits fixed by the law and taking into account the acquired data of the science, a doctor is free of his prescriptions which will be those which he considers the most appropriate in the circumstance".
The persistence of the seven days a week regime can be explained, in my opinion, by a resistance to change - which is not unique to physicians - and by the difficulty of challenging a long-standing rule in the medical community. One can imagine that other factors at play: obviously, patients prudence and of doctors before a level of proof considered as insufficient according to the standards in force; the fear of doctors regarding the judiciarization of medicine; or the influence of the pharmaceutical industry on the strategic choices by medical authorities.
Seven to four days of treatment represents 42% fewer drugs. This would result in savings of around 500 million euros for the French health system each year (based on 100,000 patients on treatment, with an average cost per patient and per month of 1,000 euros on average). Globally, the issue of cost meets ethical and humanitarian concerns at a time when 22 million HIV-positive people still do not access triple therapy.
For his part, Dr. Jacques Leibowitch pushes further the alleviation of treatments, in accordance with the code of medical ethics, and for patients who so wish. It reduces medication, depending on the case, to three, two or a day only a week. With this new protocol called "big" Iccarre, he pursues the goal of finding for each patient the right dose, both necessary and sufficient. In accordance with The principle: Primum non nocere ("first do no harm") which was dear to Hippocrates?
This was originally published here, in French. We provide this translation for your convenience, practical aspects may differ where you live.
The amazing and promising 1/2
By Charles-Edouard!
In comments, a Genvoya® not innocent at all!
This example shows how younger people are wrong not to worry about long-term toxicity, in advance. With age comes also polypharmacy (eg statins, useless but often prescribed). Now, Genvoya® has a non-exclusive booster: it is included and boosts one of our other drugs and thus we are in overdose. This also highlights a low noise, sub-clinical, but very real, toxicity.
1/2 = half-dose or 1 day out of 2?
1/2 comes from community practice, not academic. It results from a pharmacokinetic vision, complementary to the Eclipse. Many do not understand Eclipse.
So be it... The 1/2 does not lead to remission. On the other hand, it is understandable by the Septists, that is to say 99.999% of doctors and patients. Pharmacokinetics at heart, they practice it with permissive drugs (eg Triumeq®, Atripla®). And with long lifetimes, taking 1/2 pill each day or 1 pill every 2 days is quite similar; The 1/2 is a dosage adjustment. This is the A-TRI-WEEK trial, which worked very well!
I have done Mono-DTG: 1/4 of a pill (mini-Dolu), others are doing Mono-DTG 1/2 of a pill (or even Mono-IP 1/2 dose). Certainly, my preference remains for the short cycle. I liked reduced dosage also!
Efavirenz 300 mg? Why not?
In the Phase II trial (DMP-266-005, by Joel Gallant et al., Never published ...), 200 mg works better than 400 mg and 600 mg ... And what do they chose? Well ... They didn't care ... 600 mg and fuck you all! Dosage is the responsibility of doctors, not of the pharmaceutical industry ... Facing a suicide epidemic, smart people tried EFV 400 mg: it works. For some unknown reason no one tried EFV 200 mg ...Go figure ...
At the IAS 2017 conference (video here), at minute 49:25, Pr Kiat Ruxrungtham, says: we do with 300 mg and it works very well...Here is a good idea! 300 mg !!!
Note, incidentally, in this sequence, something interesting: they have done tests and offered to patients who have CNS problems with EFV 600 mg to reduce down to 400 mg without even a dosage. And it works ... Which leads him to say, in the same wake, that it also works at 300 mg. Question: If it works without problem at 300 mg, why restrict oneself to patients complaining of CNS problems only?
Synergy, a heuristic concept, with no identified mechanism, claims that some combinations work better than others. However, the dosage is never reconsidered. Thus, 3TC is set at 300 mg from its early introduction. It dates back to AZT / 3TC Bi-Therapies. Nobody ever had a commense reflection: well, with Efavirenz, maybe we can reduce 3TC a bit. As If ... There are some clever people, who have seen that Cobicistat (an hepatic metabolism inhibitor, often named: EVG booster) ALSO boosts TDF, and ask the question why do not we reduce the amount of TDF at the same time? Simple, doing so it brings not profit to Gilead.
Especially since they will effectively reduce when switching to TAF. And may be, they already have a me-too copy of 3TC (I bet you they will add another Fluor), some sort of 2F-3TC, that they will come out of their magic hat and market as an all new combo, less dosed.
And no one to look back and say, "Oh, but we used 3TC abusively, at 300 mg, for years without asking any questions."
It is clear that, today, patients are very well treated in Thailand, probably better than at home! Intelligence is not reserved for us. So Siamese or Chinese clinicians will uncover the hidden Gral: they are at work there, without you noticing. Then will appear a combo composed of 300 mg EFV + 150 TDF + 100 F-3TC (or 150 3TC), to take twice daily for 1 year, followed by 1 per day ad-vitam. Maybe even 200 mg EFV ... Why not?
And we can only then note, once again, the inanity of the ANRS. We have no ideas, they say. Yet, alternative proposals are moving forward.
You will be fattened with injectables at 10,000 Euros per year, whereas they will have nice and effective treatments at 50 Eu / year. That is crazy! After we are being told that French workers are not profitable, they are lazy! So they cut jobs, cut jobs, cut jobs ...
No need to go to Thailand: sooner than never, Greeks, Ukrainians, Cubans, Venezuelans will get at it.
In the news
...
Does Prep flops? Only 5,000 Prep users! Activists are highly disappointed! So they go at it again ...
Universal, mandatory vaccination is voted: when will come mandatory treatment? Not before the arrival of injectables... So this is coming. Here again subsidized Seronegative activists will be at work!
This was originally published here, in French. We provide this translation for your convenience, practical aspects may differ where you live.
Treat-Early: How Guidelines are misleading
By Charles-Edouard!
The doctor does not analyze the ASAT / ALAT for fun! The liver is on the front line and receives the most of toxicity! If allowed to, toxicity sets in and becomes irreversible; and if we do not want to let it do, what do we do ?! Overprescription is a real martyrisation of women's body. You were asymptomatic and immunocompetent, and, abracadabra! You're hepato-deficient ... Bravo!
Short reminder: the question is to know at how many CD4 it is recommanded to initiate treatment. Before it was less than 200, then they extended the indication to less than 350 and less than 500, then, now, less I-do-not-know-what: everyone is concerned. In a review (Should HIV therapy be started at a CD4 cell count above 350 cells / μl in asymptomatic HIV-1-infected patients?), C. Sabin showed that, in the area with very low risk, studies were indecisive (this which is hardly surprising when the absolute risk is so low). She asserted that only a comparative, randomized, trial would make it possible to decide. She considers that the START trial fulfills this role. Legitimate hope if the trial had not been, by construction, biased. The START scandal is multi-faceted: it will be our summer 2018 series! So we are not going at it here: just remember that this trial is biased, by construction.
The Morlat Report concludes in favor of undifferentiated, early treatment.
Treat early? Bullshit! Shouts the European cohort
The most recent study, the HIV-CAUSAL cohort, under our tropics, concludes to the futility of treat-early. Nobody ever mentions toxicity, obviously ... In Europe, in the area of minimal risk, the individual balance between individual clinical benefit and medico-pharmaco-induced toxicity (), is not at all in favor of treat-early. As a proof, read this case, of a patient, deceased, horribly, due to pharmaco-toxicity, in 2009.
They conclude: the beneficial effect is less than in recent randomized trials. In fact it is zero: 5j. of additionnal life in expectancy! However, in its latest version, the Morlat report omits, shamelessly, this mega-study (55,000 patients!), published in The Lancet HIV(2015). Maybe they do not read the LANCET HIV...
How did we get there?
To bias START, they surreptitiously introduced patients at high risk (pretreatment) among others, at microscopic risk. They are necessarily tipping the scales towards early treatment.
Morlat, using, as justification, the ANRS-TEMPRANO trial pushes it one step further: we will use patients from a geographical area (Senegal) with high endemicity of tuberculosis. Tuberculosis, or even its suspicion, is an indication for prophylactic antituberculosis treatment: Tuberculosis greatly raises the risk. How do we know that? Exactly thanks to the trial ... ANRS-TEMPRANO! Adding insult to injury!
The trial demonstrates the benefits of antituberculosis prophylaxis. And they would like us to believe that they recruited HIV patients at very, very low risk! It's amazing when you think about it!
Actors of TEMPRANO write an article, and, in very civilized terms (they work for ... ANRS ...), give the keys to this incredible trickery (trickery for the French, for the Senegalese, unfortunately, this is real).
This is a disputed benefit, probably zero. If this is all the more beneficial in areas of high prevalence (TB, etc.), it is therefore, on the contrary, much less beneficial in low prevalence areas. From their point of view (Senegal), the authors welcome a universal recommendation, while warning us that, in the North, this benefit is probably illusory.
Of 40 million infected, 2 live in the North. For 95% (the South) an indication extension is beneficial, while it is zero (or even negative) for the 5% that we are. In misleadingly mixing two very different health risk populations, in proportion 95% - 5%, it is obvious that the decision, taken on the average of this amalgam, is actually detrimental to us. To illustrate that , I propose to take the
TEMPRANO table, and subtract tuberculosis and invasive bacteria events, if you consider that it is a risk to which you are not exposed. The TREMPANO table also indicates that tuberculosis-disease has caused the death of 8 patients (estimated) (you are told that these are patients at very very low risk ...).
Event
Differed Treatment
Early Treatment
Tuberculosis
57
28
Invasive Bacteries
42
14
Other
10
6
Deaths (*)
26
21
Total
135
69
Let's remove what is endemic there (Tuberculosis and invasive bacteries )
Corrected Deaths (*)
20
19
Corrected Total
30
25
(*) You will notice, by the way, that they have counted patients twice: the tuberculosis, and the death that follows! (But that does not shock anyone!) We will also remove these deaths proportionally (for lack of better). There are 8 deaths (5 + 3) attributed to tuberculosis at the 57:27 ratio, ie 2: 1, so 6: 2. I spare you the calculation of small p, the risk, if any, small, with an absolute risk, very small (we are in Senegal ... Not in Pithiviers)
The average French patient, never exposed to the risk of tuberculosis bacillus and other endemic bacteria is at zero risk. The young person, without particular comorbidity, without significant immunodepression will be inflicted a triple therapy, daily, over a dozen years in excess, to avoid, hold your breath: the Senegalese tuberculosis!
Treat early: an ICCARRE booster
Think what you want, even say that they do not care a damm, you can't do anything: indeed the Morlat group, unlike the HAS, is not justiciable: you can't sue them! (HAS you can ...); the HAS remains on the 350 threshold...
My doctor, once confessed to me, long after, that he has never seen any PCP or Kaposi at 500!
This leads to ostracism towards patients-who-are-not-fooled: they are quickly excluded! Yet, if we had told them about ICCARRE, 1/7 ... Treat-early, if accompanied by Treat-better is more attractive.
We will see the economic, societal, liberticidal, coercive, toxic consequences in a future post ...
