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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.



The new dual therapies 2018

By Charles-Edouard!

The 2016 bitherapies, now validated

Yes, the 7/7 bitherapies are 'lightening', let's say a de-escalation, made possible with the arrival of DTG. Unlike intermittence, they do not bring you any closer to dynamic remission, unless you validate them in 4/7 mode (or better).

We have already presented DTG/3TC, DTG/RPV, DTG/F-3TC and NVP/RAL. Please read that post. In 2018, DTG/3TC (and a fortiori DTG/F-3TC) and DTG/RPV passed the validation tests, funded by the industry, with flying colors. The result is two co-formulated products: JULUCA ® (DTG/RPV) and soon DTG/3TC which is announced here, following the 2 Gemini trials, with 1400 patients.

Nothing new under the sun and our biotherapies of choice are validated, hurray! Well... Yes, because for patients who do not know the eclipse, the risk was to remain for years and years on superfluous triple therapy. Obviously, it takes the edge off the zinzins like Genvoya® or SYMTUZA® ; the transparency commission (HAS) has also rejected SYMTUZA® and Descovy® by giving them a shitty ASMR... Well...

3 new dual therapies

Today let's highlight 3 new bi-therapies. Indeed, the power of DTG invites clinicians to new approaches, including the question of the relevance of doses or other tricks (boosters)

Nevirapine 200mg + Lamivudine 300mg

Yes, the VerxVe trial shows that the admissible threshold is not 4,000 ng/mL as the Morlatexpert report still claims, without justification(and for good reason...). This leads to this terrible admission, found by chance, on the Saint Antoine assay reports:

In a word, the recommended dose of 4000 Nevirapine(though not whey...) is wrong by at least a factor of 4

Dr. Lanzafame had already reported great success with NVP 200 mg in maintenance. He went further and removed TDF (alternatively ABC), putting his 9 patients on NVP/3TC.

He reports on this in the article here:
'Deep' antiretroviral de-intensification, a strategy to avoid drug interactions and long-term adverse effects of HAART.

Obviously, compared to dynamic remission, this is a pity... But let's think about those millions of patients, often Chinese, on NVP, and who are worried about the use of TDF.

There are solutions, we must explore/validate them

It would be smarter, cheaper and easier to deploy than DTG/3TC, whose favourable price in 'poor' countries is still pending.

Efavirenz 200mg + Lamivudine 300mg: bis repetita and a surprise...

We take the same and we start again: this time with EFV 400 mg then 200 mg, with the suppression of TDF (or ABC): that's what makes you a low cost and low toxicity maintenance biotherapy. A wink to one of our readers who is concerned about this subject.

No need to switch all France from EFV to DTG

Lanzafame remains a pharmacokineticist at heart. Eclipse is not yet his thing, even if he is kind enough to cite ANRS-4D as inspiration, and to write:
The hypothetical effective concentration... My eye!

We ask the great chief of synergies (Aka Leibo) and we learn that Yes! EFV 200 mg is good! and in 1/7 what's more! (with TDF/F-3TC/DDI)... And even better, a patient of African origin (with the right cytochromes) does 1/7 with only 100 mg of EFV (in Quadritherapy)

Lanzafame, by pushing open doors, is not at the end of his surprises!

The end of the end: DTG/ATV, candidate for 2/7 (or even 1/7)

The question is how to use DTG in 1/7: it's not written on the brochure! in Mono-DTG, I don't doubt those who manage to do it; I didn't succeed(I may have made a mistake by putting it in a capsule, go figure...). DTG/3TC in 1/7 does not tempt me too much because in case of failure you get mutation 184, which you then have to clean by drowning. I don't have the time... So I had to find something that fits well... And there ATV is a very good candidate because it is a DTG booster, in addition to being well tolerated, at this homeopathic dosage (1/7...). For Leibowitch, it will be without the booster (ritonavir), so, obviously, it is attractive! The 2 highest barriers to resistance and a pharmacokinetic synergy at stake: here is a good candidate!

We mentioned it during our staff meeting at the Salpêtrière Hospital... And Pr Katlama agreed... So we keep him for OMNIBUS: it's my new hobby! Especially since I'm not done with DTG yet!

In fact, the only thing that bothers me is the DTG/NVP incompatibility: it's irremediable... Well, we'll see with the dodecatherapy, currently being explored, in view of the 1/15.

Finally, to have tried it, this ATV passes finger-in-the-nose: it is really a track to dig.

Bi and intermittence: comparative table

(added on 10/01/19) From DTG, there are 3 Bi options (DTG/RPV, DTG/3TC, DTG/ATV), and the question arises which one is the most favorable to intermittence. Note: the Bi + Intermittence coupling has only been explored by patients, in autonomous mode, or by Leibowitch. To date, the corresponding clinical trials are in preparation (OMNIBUS and OMNIBUS-Bicycle)
From NVP, there are 2 options (NVP/3TC, NVP/RAL). RAL is the source of the Achilles' heel, so it is not to be retained. NVP/3TC remains, published by Lanzafame.

I add (on 10/01/19) a comparative table:

Bi	Pills	Side effect	Cycle Explored	Objective Cycle	led to 2/7 ?	trial planned	preference
DTG/RPV	1	Yes (psy)	not tested	4/7	No	OMNIBUS-Bi
DTG/3TC	1	No	4/7 (stand-alone)	4/7	Yes (*)	OMNIBUS-Bi
DTG/ATV	2	No	2/7 (Leibowitch)	2/7	yes	OMNIBUS-2D
NVP/3TC	2	Rare	No	4/7?	Yes (*)	OMNIBUS-2D
NVP/RAL	4	Yes	No	No	No	No

Yes (*): with TDF added

Charles-Edouard! The Book...

It's not going anywhere, because I'm in charge of OMNIBUS and you can't write history and tell it at the same time, Ah, well... Yes, we can. Well... I don't have time...

In the news

- read this article with interesting data on the Eclipse; it dates from 2015 and has data on a whole population of patients, not only 'top' patients; and the eclipse, relentlessly from 15 to 21 d....

- you can learn a lot from this article: Is dolutegravir pricing fair? A comparative analysis of price and country income level in 52 countries

- another interesting article: Risk of Viral Failure Declines with Duration of Suppression on HAART, Irrespective of Adherence Level: it shows that, after the first 1-2 years, the risk of rebound decreases even with poor adherence: this helps to explain, graphically, why it is necessary to wait for a year of undetectability before starting 4/7

- after the Levothyrox scandal, here is Androcure, and a new brutalization/medicalization of the woman's body.

The French genius

I like Nolween Leroy, here with Renaud Capucon, in the mythical I'm calling you (Bagdad Café)

The prize goes to J.P. Gaultier and his brilliant Freak Show! The ICCARRians will pay attention to every moment: a surprise awaits them, in the form of a wink, which will warm their hearts. Many thanks to our national Jean Paul, of whom we are so proud! See the trailer here, and enjoy it for the holidays!

Feel free to comment, like, share and use

good weekend, good stuffing and not too many meds ... Huh?