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Saturday, April 9, 2016

A guide to Bitherapies

A guide to Bitherapy

By Charles-Edouard

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



There you go! You have to try hard, but, this iss coming! You have eliminated that big s**t of Tenofovir. That is a huge gain! Now you have everything at hand for future progress: Tivicay® monotherapy and / or short cycle. Keep on the good job!

Why dual therapy? Is it better than monotherapy?



The strategy Triumeq® -> Dual Therapy (Tivicay® based) -> Tivicay® Monotherapy -> 4/7 (mono) and 1/7 (Hypodolu) has a definitive advantage over any other: patients can move forward at their own pace, without bumping into the medical establishment (poisoners in a white coat ...). Once on Tivicay® based Dual Therapy, all doors are open. At the sole discretion of the patient and (possibly, but not necessarily) of their physician.

Door to freedom, the patient's freedom away from the tacit alliance between doctors and pharmaceutical-poisoners-firms, it faces a strong reluctance of poisoners/doctors: this is how we identify them easily.

Dual therapy has a favorable institutional tail wind. See LAMIDOL trial

Commercially, the manufacturer increases their margin by combining a diamond (dolutegravir) with glass beads (eg. Abacavir + Lamivudine) then sells dolutegravir 50% higher!

Hence the idea to change the glass beads from time to time (see the SWORD-1 SWORD-2 trials)

France plays one step ahead and Tivicay® monotherapy gaining ground. Dual Therapy based on Tivicay ® is the entry level option.

Dual therapy based on Tivicay® and other



Here, we discuss Tivicay® based Bitherapies. Indeed, it appears from EACS-2015 and the work by Pr. Katlama (Salpêtrière) that prior use of Raltegravir (or elvitegravir) compromises the chances of switching to dolutegravir monotherapy, which remains our intermediate goal. RALTEGRAVIR (Isentress ®) based Dual therapy should therefore be avoided.

Tivicay® + Emtriva®: our favorite



Emtricitabine is nothing more than fluorinated Lamivudine. Except for one Fluor atom, this is exactly the same molecule ... The name difference between Lamivudine (3TC) and emtricitabine (F-3TC) is confusing.
In practice, we can replace one by the other, without further consideration. The equivalence and interchangeability between the two molecules (the fluoridated, the other not) is recalled in the Morlat report. It is also recalled by the WHO:

Pharmacological and clinical equivalence interchangeability of lamivudine and emtricitabine

It is precisely because it is equivalent, in practice, that trials are conducted with lamivudine (exists as a generic, therefore less expensive). The validity of the very good results also applies to Emtricitabine (Emtriva®) This interchangeability (equivalency) may be misleading. But in fact, it is the same ...

It naturally follows Tivicay® + Truvada (TDF + 3TC-F) and has all the advantages of Tivicay® + Lamivudine. It has another advantage: it will never coformulated.

Tivicay® + Lamivudine (Epivir ®)

: the most popular

HYPO-DOLU EACS 2015 Dolulam Dolutegravir Dr jacques Reynes Montpellier
Advantages:
- Inexpensive
- No meal obligation
- No known serious side effects
- No specific biological monitoring
- No effects 'psychotic'side effects

Thusfar it is not coformulated, it opens the way for the monotherapy Tivicay®: just leave the Lamivudine on the shelf. This is an excellent transition between the combination therapy and Tivicay® monotherapy. Ideal for ensuring the good tolerability of dolutegravir (Tivicay®) since Lamivudine is considered innocent of everything. Prof. Reynes , who chairs one of COREVIH, is an ardent promoter.

Tivicay® + Edurant ® (Rilpivirine): coformulated but uninspiring


Preliminary tests were conclusive and commercial qualification trials are ongoing (sword1 & sword2).

The future of this combination therapy is anticipated: coformulation (only 1 pill / day.) And FDA approval. As a key holder, a great promotional campaign by the manufacturer: How to promote maintenance of combination therapy without getting the message out that maintenance is done differently than induction (initial treatment)?

So we'll see tons of arguments to explain maintenance in a population thus far held in ignorance.

disadvantages:

- expensive
- meal obligation
- Harmful (Rilpivirine)
- Coformulation (Tivicay® therefore becomes inaccessible)
- Effects 'bizarre psychotic' (almost as frequent as with Atripla)

Tivicay® + Nevirapine: not interesting, stay away



Approximately 10-15% of patients do not tolerate nevirapine. Even if it is tolerated, it has no advantage compared to Tivicay® + Lamivudine. It originates from Raltegravir (Isentress®) + nevirapine (Viramune) Dual Therapy, which had good results, by Raltegravir substitution with Tivicay®, which is more powerful.
We now know that Nevirapine induced a 30% decrease of Tivicay® concentration. It's enough to shy away your basic clinician. (Read here)

You will notice that even a reduced concentration of 30% does not affect the maintenance of undetectability:
the concentration obtained with 50 mg is unnecessarily high for maintenance.

Good weekend and good fuck!


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

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