Practical Guide to Mono-DTG
Work in progress
Unlike ICCARRE 4/7, recommended by ANRS, Dolutegravir monotherapy (Tivicay®) is experimental. For Tivicay®, you need a prescription, so it's something that you should work out with a doctor. Which one? This is experimental, so not just any doctor will do... In France, you may want to go to Pr Katlama (Salpêtrière, Paris), Dr. Lafeuillade (Toulon), Dr. Hocqueloux (Orleans); Spain: JL Blanco or E. Martinez (Barcelona); Italy: Dr. M. Lanzafame; Germany: Dr. Oldenbüttel. Also, the MONCAY trial is recruiting. Think about it ...
One distinguishes Mono-DTG as first line, in patients new to any treatment, and maintenance Mono-DTG.
First line Mono-DTG, in naïve patients
Dr. Lanzafame does it on patients with a VL <100,000 copies and a perfectly wild virus: see here. Dr. Lafeuillade also claims to do it... It's working well, with carefully chosen patients.
Dr. Lanzafame has published excellent results, with patients whose CV <100,000 and the perfectly wild virus. There is no evidence that these conditions are necessary; Of the twenty or so patients who have tried this, we know no failure.
Good compliance is important. In the ACTG A5353 trial (DTG + 3TC), which has one molecule more than Mono-DTG, 3 failures due to poor compliance were observed ...
So there is reason to believe that compliance is important in Mono-DTG, at least initially.
Mono-DTG maintenance (switch ...)
Unlike first line treatment, there is an influence of treatment history. 5 Pitfalls are to be avoided:
- The Achilles Heel: having used RAL and / or EVG in the past
- The Hunchback Trap: coming from a NNRTI, worsen if it's Nevirapine (Viramune)
- Lack of adherance
- Failure to monitor with frequent VLs
- Have had previous failures or limited options (history, genotype, ...)
It is silly to claim that the Mono-DTG is not used or that it does not work
The first pilot trials have highlighted traps, which, if avoided, reduce the failure rate to 1-2%.
The Achilles heel
It is explained in the posts:
It is defined in a simple way, sometimes misunderstood:
Achilles' heel = having used Isentress®, Stribild® or Genvoya® in the past.
That's all, it's simple, it's the mere fact of having used these (including with virological success, ie undetectability); those who used them, even without failure, are concerned.
If I had a virological failure with Isentress®, Stribild® or Genvoya®, am I counted as Achille's Heel? Strictly speaking no. An Achille's Heel is a serious weakness that goes unsuspected, you are going to war as if nothing had happened, wrongly. If you have had a virological failure with Isentress®, Stribild® or Genvoya® you are definitely not eligible for Mono-DTG: just forget it!
The Achille's Heel is to have used, without failure. About 1 out of 5 patients affected by the Achille's heel, failed (rise in viral load), and conversely 1 failure out of 2 is attributable to the Achille's heel.
If this is relevant for you, think carefully, learn, ask ... Ask about ICCARRE (recommended by ANRS), it may be better fitted.
It is defined in a simple way: use of an NNRTI (see list below) when switching to Mono-DTG (or, possibly, DTG + x or even DTG + x + y); it is potentially more marked if the NNRTI is nevirapine (Viramune®)
The risk is poorly measured, poorly characterized, but easy to cover: there is no point in guessing this or that ... Just remember the following pharmacokinetic rules (see insert label):
- breaking the tablet, for example between teeth, increases the bioavailability
- take with a meal increases bioavailability
- do not take other medications / supplements within the hours before or after
- the label indicates that the taking of 2 tablets is possible.
This decision should be sufficient to compensate for the transient deficit during the switch. In first approach, this deficit does not last more than 1-2 months.
As Dolutegravir can induce a depressive state (reported by about 10% of patients, in use in the long run), we can remember the pharmacokinetic rules above, if we want to lower the concentration a little, after having verified that the switch is going well.
Good adherance is important. In the ACTG A5353 trial (DTG + 3TC), which has one molecule more than Mono-DTG, 3 failures due to poor compliance were observed ...
So there is reason to believe that adherance is important in Mono-DTG, at least initially. Anyway, for all that is experimental, the good adherance is important (if not, in case of failure, you do not know what is what...)
In all pilot and experimental trials, frequent CLs were used (eg, month-1, month-2, month-4, month-6, etc.). Those VLs does not reduce the risk of failure, they reduce the potential consequences. In case of rebound, one must see quickly with the doctor and take corrective action without delay.
Have had previous failures or limited options (history, genotype, ...)
Mono-DTG is experimental. It should therefore be avoided if there had been at least one virological failure with other Integrase Inhibitors: EVG or RAL (ie Isentress®, Stribild® or Genvoya®). In such a case, it's Niet, Niet, Niet!
In addition, if the genotype or history (eg failures) prohibits comfortable alternative options (eg Eviplera®), then think twice ...