Friday, November 11, 2016

time to rebound

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

An activist activist, unaware of ICCARRE, opens the box:

Hill has suggested that reservoir reductions on the order of 5-6 logs (100,000-1 million fold) would be necessary to delay viral load rebound for 30 years [...], while a yearlong delay would likely require a drop of at least 3 logs (1,000 fold). [...] a new model was published that argues that significant delays in viral load rebound might be achieved with far more modest declines in HIV reservoir size.
[...] produces a result of one successful reactivation of latent HIV every six days, considerably less frequent than a previous estimate [...]
The researchers extrapolate that a yearlong delay in viral load rebound might therefore be achievable with a reduction in the HIV reservoir of 60-70 fold, a more optimistic scenario [...]
significantly lowered HIV reservoir levels would also allow for a more direct assessment of the impact on time to viral load rebound.

Blessed are our readers: here we also look at how to benefit, in practice, from what the facts show. Richard Jefferys seems to ignore all of the short cycle and years of pharmaceutical remission. This is even more laughable now that our good Siliciano recently acknowledged his errors on reservoir content, hardly capable of initiating a rapid reactivation.

The time needed to rebound is the keystone of ICCARRE 1/7. We started this discussion here, and show its practical use there.

We can now visualize the time-to-rebound

The DNA method tels us nothing. We will still devote a post just to have the pleasure to grill down the Rouzioux criteria, which caused so many pain to patients.
Mykola Pinkevych in HIV Reactivation from Latency after Treatment Interruption provides a better understanding.

An analytical interruption can be done easily, is a bit tedious, and sheds much light.

Pointless! said J. Leibowitch: since we know how to do 1/7, why bother with an analytical interruption!
He has a point... If we have better things to do, let's peep at the results of scientific research. There are a few trials, duly documented, with a hundred of patients:

Author	Date	Titre	Lien
R. Davey / A. Faucy	1999	HIV and T-Cell dynamics after	read...
Marek Fischer	2003	HIV RNA in plasma rebounds within days	read...
Mark T. Bloc	2006	The Role of Hydroxyurea ...	read...
Rothenberger	2012	Abstract_Brief_Interruption	read...
Rasmussen	2014	Panobinostat_latentvirus	read...
Kroon & Ananworanich	2016	160717 Ananworanich Abstract 10535	read...

The time-to-detection: 21 days. on average!

To find the time to detection, we have to dig in eradication studies, since, at the end, they do an Analytical Interruption (the only valid method...), and, look at control patients. And, as the intervention is useless, why not consider also the patients that did undergo the failed reservoir intervention! See Ananworanich presentation.

Remember the pathetic sales pitch by Pr. Rouzioux-of-the-criteria, she does not mention it! Whichever: she does not know and this is incompetence, or, she knows, but prefers to wrong the audience.

The discreet sponsor does not mind... What about you?

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

Comments

Anonymous 14 Nov. 2016

Hello,

My name is Joey and I don't really know how to contact the author of this blog, so I'll try it here :)

I'm HIV positive for 3 years now, probably. I'm treatment-naive. My last CD4 count was 380, VL 280 000. I feel generally unwell for almost a year. I don't know if it's for HIV, but I have A LOT of symptoms. For example: daily sweating, itching all over my body, tight chest, occasional dry cough, vision problems, digestive issues, weight loss...

I'm thinking about finally going on ARVs. Would you say I'm a good candidate for Tivicay monotherapy? My doc is of course against this (I'm in Eastern Europe). He would recommend it just with Edurant. Do you think it would be better to start dual therapy (Tivicay + Edurant) and then to stay just on Tivicay? Or could I benefit just from Tivicay? I haven't had any gene testing done.

Thanks so much in advance!

Charles-Edouard 14 nov. 2016

Hi,

Trials on Tivicay monotherapy, or bitherarapy with Tivicay, are promissing. They have been done with patients whose VL was lower than 100.000; So yours is a bit high compared to published trials.

It is a bit higher than the generally advocated limit for Edurant+ truvada (aka Eviplera or Complera).

This is relatively unimportant since your initial treatment does not have to be your maintenance treatment.

Therefore you may start on about anything as long as you can gradually move forward to a maintenance regimen that suits your lifestyle.

if 7/7 suits you here is a sample course:
- start with Triumeq (DTG/ABC/3TC) for 6 months
- drop the ABC , therefore Tivicay + Lamivudine (DTG/3TC): this dual therapy is considered very safe (for 6 months or more)
- maybe drop the 3TC for a Tivicay monotherapy : trials results are satisfactory but there has been a few failure, so frequent VL should be available to avoid uptake and resistance

If you would prefer a 1/7 route
- start with Atripla (EFV/TDF/F-3TC) for 6 months (maybe a bit tough at start)
- switch to Eviplera (RPV/TDF/F-3TC), 7/7 for 6 months
- move to short cycle 4/7 (skip Friday, Saturday, Sunday) for 1 year
- move to 3/7 with frequent VL monitoring at first

Those are exemples.

if you would want alternatives and/or discuss with doctors who have expertize in maintenance strategies please see our page:
https://charles-edouard-ma-liberte.blogspot.fr/p/medecins-allegeurs.html

Dr Lanzafame is may be not too far from you and masters these Tivicay Monotherapies
Do not hesitate to post comments if you need further assistance

Joey 20 Nov. 2016

Hello Charles,

thank you for your reply!

I have a question regarding Triumeq. Do you think it would be possible to have it prescribed in 3 separate tablets (DTG/ABC/3TC)? Hopefully this is not going to be a problem in my country.

Regarding 1/7 route, I would prefer it to 7/7, of course. But I've heard a lot of information about NRTI and NNRTI (in Atripla or Eviplera) being quite damaging to human body. I'd rather avoid those and hopefully manage to get to just using Tivicay as a monotherapy. What do you think? Are NRTI and NNRTI actually that harmful?

Thanks in advance for response.

Charles-Edouard 20 Nov. 2016

Hi Joey,

Your question is 2 fold and is about strategies that are still in experimental stage. Whatever experimental you intend to do, you should have a strict policy of more frequent VL, typically every 2 months, at the begining only. You may want to keep us posted, so that we may share your experience with others.

Which ever route you choose, your first leg will be a 6 months course of tritherapy (because your VL commands this). And Eviplera (RPV/TDF/F-3TC) should normally not be that choice. Tivicay+Truvada (DTG + TDF/F-3TC) is one combo that suit you request for a 'split' combo. After the 6 months course, you can then decide to go towards Tivicay Monotherapy (ideally with a Bitherapy stepstone) or towards 4/7 (with possible extension to 1/7): so your choice will be around mid-2017, at the earliest. By that time a good number of trials will be published and may guide you.

So T&T is way to postpone the choice, while leaving all options open.

Through this English version of the blog, you get a window to what is going on in France, without the need to participate in French discussion: let me wrap in a few words:
- Eviplera is higly praised and safely used in 4/7 (see ANRS-4D trial). It is also experimentaly used in 2/7. Tolerability is very good for a high proportion of patients. Toxicity gets reduced by the short cycle.
- Tivicay monotherapy is highly praised, but there has been a few failures (rare, but still) in trials. Experimental extension to 4/7 is undergoing and doing well; considering that 3TC is not toxic, it may be a good addition to ensure success.
- Tivicay with either Truvada (DTG + TDF/F-3TC) or in the Triumeq form (DTG/ABC/3TC) is being experimented all the way to 1/7 (very limited number of volunteers)

Strangely enough the best tolerated a combo is, the higher the success rates in short cycle. I guess this is because short cycle candidates, with toxic combos, are more prone to skip more than the short cycle schedule allows for, and, thus fail...

My gut feeling is that all these strategies are succesfull when handled in a step wise progression with at least 6 months (12 better) validation periods. So, whichever your target is, you have plenty of time.

Keep us posted

Joey 21 nov. 2016 à 05:39

Hi Charles,

thanks for all the info, it's really appreciated! I was asking about a split combo because Triumeq is 3in1-pill regimen and after 6 months I would drop the ABC, as you suggested. So I would then need to have my prescription changed to just dolutegravir+3TC, or even start with three separate pills from the beginning, and do this "incognito" :) But I'll see what my doctor says, he seems quite open-minded and maybe he would approve.

The thing is, I don't really know how does it work with my insurance company. Is it more expensive for them to pay for 3 pills vs. one-pill med Triumeq? It wouldn't even make sense for them - someone wanting 3 pills instead of 1. An ideal scenario for me would really be Triumeq first 1/2 year and then bi-theraphy - still not sure if my doctor would approve. But I think I can talk him into that :)

I think though, insurance co. would be probably happy to change from Triumeq to just dolutegravir+3TC as that would be cheaper, wouldn't it?

Regarding Truvada, I would rather not take it. I've heard it can cause significant bone density loss... More so than other ARV drugs. I might be wrong, but that is what I've learned from various sources.

Thanks again!

5 comments:

AnonymousNovember 14, 2016
Hello,

My name is Joey and I don't really know how to contact the author of this blog, so I'll try it here :)

I'm HIV positive for 3 years now, probably. I'm treatment-naive. My last CD4 count was 380, VL 280 000. I feel generally unwell for almost a year. I don't know if it's for HIV, but I have A LOT of symptoms. For example: daily sweating, itching all over my body, tight chest, occasional dry cough, vision problems, digestive issues, weight loss...

I'm thinking about finally going on ARVs. Would you say I'm a good candidate for Tivicay monotherapy? My doc is of course against this (I'm in Eastern Europe). He would recommend it just with Edurant. Do you think it would be better to start dual therapy (Tivicay + Edurant) and then to stay just on Tivicay? Or could I benefit just from Tivicay? I haven't had any gene testing done.

Thanks so much in advance!
ReplyDelete
Replies
AnonymousNovember 21, 2016
Hi Charles,

thanks for all the info, it's really appreciated! I was asking about a split combo because Triumeq is 3in1-pill regimen and after 6 months I would drop the ABC, as you suggested. So I would then need to have my prescription changed to just dolutegravir+3TC, or even start with three separate pills from the beginning, and do this "incognito" :) But I'll see what my doctor says, he seems quite open-minded and maybe he would approve.

The thing is, I don't really know how does it work with my insurance company. Is it more expensive for them to pay for 3 pills vs. one-pill med Triumeq? It wouldn't even make sense for them - someone wanting 3 pills instead of 1. An ideal scenario for me would really be Triumeq first 1/2 year and then bi-theraphy - still not sure if my doctor would approve. But I think I can talk him into that :)

I think though, insurance co. would be probably happy to change from Triumeq to just dolutegravir+3TC as that would be cheaper, wouldn't it?

Regarding Truvada, I would rather not take it. I've heard it can cause significant bone density loss... More so than other ARV drugs. I might be wrong, but that is what I've learned from various sources.

Thanks again!

ReplyDelete
Replies