Forum Replies Created
-
AuthorPosts
-
The official received medical advice for GT1 folks who have already treated with an NS5A is not sof+led or sof+dac. It is what the AASLD and Jonathan’s consultant recommended, ie. simeprevir, sofosbuvir, and RBV for 24 weeks.
I do agree that sof should form the backbone of Jonathan’s next tx, because it has a high barrier to resistance unparallelled by any other drug on the market, and it wasn’t used last time. I see no reason why sim should not also be used because no NS3 RAVs were found. The question I have is about whether the 3rd DAA should be an NS5A or ribavirin and which one will achieve higher efficacy? The answer, so far as I can make out, is that it depends. The use of an NS5A to treat NS5A RAVS requires analysis ot the RAVS present and targeted therapy with specific choice of NS5A to be used. One size does not fit all, as yet.
I want to add that I think this subject is really an important one for anybody currently treating with an NS5A, ie. most people. Fine if that tx leads to SVR first time round. If it does not then we, and that includes me, are going to have a steep learning curve to deal with our own NS5A RAVS.
dt
“But the point I really want to make is that a virus protein might escape one drug, but it can still be clobbered by another one which fits the pocket in a slightly different way – with or without the mutation. So in Jonathan’s case, a different NS5A inhibitor from elbasvir could still work on his NS5A RAV.
As there are lots of new antivirals coming on-line, this means lots more possible combination treatments. But it then becomes a question of doing many clinical tries to see which actually work.”
I totally agree Vororo. But WHICH NS5As will work for the types of NAVs that Jonathan has, that is the significant question that clinical trials have not yet answered. In the meantime, what is he to do? Just try any NS5A that’s not elbasvir and hope for the best? And if that is not the one that works then does he end up with even more kinds of NS5A RAVS to deal with next go round? What if there are many kinds of RAVS present and no one NS5A inhibitor will kill them all? Do you take more than one NS5A? What about the dosage required? That’s a lot of unanswered questions.
dt
Here’s a recent write up:
“Management of patients with hepatitis C virus resistance–associated variants to NS5A inhibitors: Where are we now?”
http://onlinelibrary.wiley.com/doi/10.1002/cld.507/full” We do know that almost all patients who fail to achieve SVR will have resistant variants, and if treatment involved NS5A agents, these patients will have long-lived RAVs, most likely for years. The screening of all patients who previously failed a regimen containing an NS5A inhibitor is recommended when considering retreatment with a regimen containing an NS5A inhibitor. It is not a matter of if a RAV will be found, because that is almost a given. The specific RAV and the number of RAVs are critical in determining if the patient can be retreated with an NS5A again. The likelihood of SVR can range from 30% to 100% if retreated with a regimen containing an NS5A, depending on these specifics. To further complicate the issue, not all NS5A agents have the same liability to the same RAVs, making it even more critical to know what variants are present.”
dt
Jonathan asked:
“My specialist has suggested a 12 week course of sofosbuvir/simeprevir/ribavirin – what are your thoughts? Any alternative options that may have greater efficacy?His specialist is in line with the AASLD recommendations for his case if he is cirrhotic:
“For patients who have NS5A inhibitor RAVs detected and who do not have NS3 inhibitor RAVs detected, treatment with simeprevir, sofosbuvir, and RBV for 24 weeks is recommended.So, even given that resistance is relative, what do you know that allows you to say with any degree of confidence that an NS5A in the combo would have greater efficacy than ribavirin against NS5A RAVS?
dt
From theAASLD guidelines:
http://www.hcvguidelines.org/full-report/retreatment-persons-whom-prior-therapy-has-failed“Recommended regimen for patients in whom previous treatment with any HCV nonstructural protein 5A (NS5A) inhibitors has failed (including daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir plus dasabuvir).
For patients with minimal liver disease, deferral of treatment is recommended, pending availability of data.For patients with cirrhosis or other patients who require retreatment urgently, testing for resistance-associated variants that confer decreased susceptibility to NS3 protease inhibitors and to NS5A inhibitors is recommended. The specific drugs used in the retreatment regimen should be tailored to the results of this testing as described below. Treatment duration of 24 weeks is recommended and, unless contraindicated, weight-based RBV should be added.”
“NS5A RAVs don’t necessarily render NS5A inhibitors useless because resistance is invariably relative.”
Hi Doc,
I can’t see how an NS5A inhibitor is going to kill off an NS5A RAV. I am not sure if it is valid to compare the mechanism of antibiotics with the mechanism of the DAA’s.
I have no medical training, but my simple understanding is that each class of DAA inhibitor is like a gate which closes off one path the virus can use if it mutates. If you have 3 DAA’s of different classes which close off all 3 gates then the virus is basically f*****. But if you have NS5A RAVS and use a combo of 3 DAA’s then the NS5A gate is rendered ineffective for them. There’s still a good chance that the other 2 gates will stop the virus including the RAVs, but not as good a chance as if all 3 gates were closed. The virus is highly mutagenic and will escape if it possibly can.There is not a lot of data on retreatment with an NS5A inhibitor. Here is one study on retreatment with Harvoni:
http://www.natap.org/2015/EASL/EASL_26.htmI think it is just too early to really know until real world data starts to come in. Maybe by that time there will also be more new drugs and trials specifically to find out what will overcome NS3 and NS5A resistance.
dtOh I forgot about that with the blood test. Sorry. However my doc told me that any liver panel blood test would show signs if my liver were to be going into cirrhosis. I am 65 so I have been paranoid every year about my liver suddenly deteriorating before the meds arrived. So if you had any blood test in the last year after your scan and there were no significant changes, I think you should be fine.
dt
Hi Jill,
If you can’t get a fibroscan in time there is an alternative based on a blood test. I think I saw details of that somewhere on this site and a comparison of the 2 kinds of diagnostics.
IMO you can never be too careful when dealing with the HCV virus. Even in these days of better drugs, a cure is not a given. So getting all your ducks lined up in a row is the way to go,
dt
Yes, it is possible, though unlikely. Progression of hepC liver damage is not linear. It is known that sometimes for no reason the damage just accelerates, especially if you get into the 60+ age group.
At the same time, the fibroscan is known to be more accurate at either end of the scale than in the middle. You don’t give the actual fibroscan numbers you got but it is possible to get a variance of about 2 on an annual fibroscan reading without your level of fibrosis really changing. At the time of the scans it is unlikely that you had cirrhosis though. The machine would have detected that.
So I think it is up to you if you want to do another fibroscan, mainly for your own peace of mind.
dt
Excellent article Alsdad. Finally somebody is laying out the playing field the way it actually looks.
“But many of the middle-income countries with a high burden of hepatitis C, such as China, Brazil, Ukraine and Latin America, will continue to be excluded by the terms of voluntary licensing agreements from obtaining Indian generics – unless they pursue compulsory licensing. Dr Hill reminded the conference that the South African government’s threat to use compulsory licensing had been critical in opening the way to lower antiretroviral drug prices in the early 2000s.”
“In the case of hepatitis C treatment, people could take matters into their own hands without waiting for governments. In Australia the FixhepC buyers club is working to assist individuals in buying generic drugs to treat hepatitis C”
So the world has the means to end the rationing of hepC drugs. Ie. use compulsory licensing – an internationally legal mechanism, and/or set up buyers clubs. Of the two, compulsory licensing is the more comprehensive approach for a country to gain the means of eradicating hepC. So you have to ask – why wouldn’t any country with a large hepC population follow South Africa’s lead and at least make a credible threat to introduce compulsory licensing? The way has even been paved for them to do so without the threat of international trade sanctions. Where are their financial spending priorities if not on a public health epidemic? I suspect that therein lies the answer.
dt
Yes, the South African government fought Big Pharma and held their ground even when the US weighed in with threats of trade sanctions. Gotta admire their guts. Well, they had dead bodies stacking up in the streets so what else to do?
They eventually won the right to import and use cheaper generic HIV medicines which were still within the 20 year patent protection term. So there is no need for us nowadays to re-invent the wheel. It has been done successfully already and the legislation which allowed it is still in place.
Which brings me right back to the question that just won’t go away:
Why is no other country (with the possible exception of Australia) stepping up to the plate to end the price rationing of HCV drugs by importing generics?
dt
——————————–I have lifted more or less verbatim what I think are the key passages of the Patents Law saga between South Africa and Big Pharma.
“In February 2001, the Bush Administration reaffirmed that the United
States would not raise any objection if WTO (World Trade Organization) Members taking steps to address major health crises “availed themselves of the flexibility” afforded by TRIPS (Trade-Related Aspects of Intellectual Property Rights).”From the standpoint of international patent law, the key legal issue underlying the South African controversy was whether the explicit authorization of generic imports of patented pharmaceuticals complied with TRIPS. The South African experience brought the potential tension between patent protection for pharmaceuticals and public health concerns to the forefront of public awareness. It triggered a global debate about what should be allowed and what should be prohibited under TRIPS in order to preserve the incentives for investments in research and development of pharmaceuticals, while still allowing countries the flexibility to respond to public health crises as they deem fit.
The Doha Declaration strives to reconcile the TRIPS agreement with efforts of WTO Member States to protect public health by reaffirming their right to use “the provisions in the TRIPS Agreement, which provide flexibility for this purpose” (Article 4).
In Article 5, the Doha Declaration addresses the issues mentioned above and clarifies that each WTO Member (i) has the right to grant compulsory licenses and the freedom to determine the grounds upon which such licenses are granted, (ii) has the right to determine what constitutes a national emergency or other circumstances of extreme urgency (the HIV/AIDS crisis is explicitly recognized as a case of emergency or urgency), and (iii) is free to establish its own patent exhaustion regime without challenge (and thus free to allow generic imports).
Sir,
I have started tx and I am just getting on with it quietly. The last two times I did tx publicly, mainly on the medhelp board which was a lot better then than it is now. At that time it was the right thing for me to do. After getting the bad news twice, this time I am trying my best to minimize my own personal stress and drama and think about it as little as possible until the time comes for the SVR24 test.
dt
LG
So glad to hear that things are at last working out for you. I think you’ll be fine now and hopefully never have to see that bastard consultant again.
Now for your curiosity and entertainment, here’s this:
Is Your Liver Specialist a Psychopath?
https://en.wikipedia.org/wiki/Psychopathy_Checklis
dtYes, note that he is being investigated for securities fraud, not price gouging.
Brings to mind the notorious Al Capone who was never brought down for any of his heinous crimes but finally stopped for something as mundane as tax evasion.
So Gilead’s business dealings better be whiter than Persil Extra.
There’s more than one way to skin a cat.dt
I’ve been to the citizens Advice Bureau. Because it is NHS they refer to PALS. PALS will hum and haw because they usually advocate for NHS patients who are dissatisfied with treatment that they have already received which they have a complaint about. If the complaint is about treatment not received, using drugs that are not NHS supplied, then good luck with that. Somebody might have some luck with this process but I didn’t.
The UK is famously a multi-cultural society. Indians, Pakistanis, Jamaicans, Arabs, East Europeans, Chinese, etc., they are all here. They mingle and they also have their own core communities. Handouts of any kind are not part of their culture. They expect to pay and are pleasantly surprised if they don’t have to.
Anyway, as to how many UK patients will go for the generics, only time will tell. Most of them are currently being disabused of their belief that they will get access to free treatment for their hepc before they die. As time goes on, disillusionment sets in and the penny drops, what will they do then?
The threat of death transcends all cultural norms. I saw an entry a while ago which moved me greatly. This person said something like, and I hope they don’t mind if I recall it, “I will crawl over broken glass to get my meds”
Do you really think that a person who feels like that is going to sit complacently watching the NHS fiddling while Rome burns.dt
-
AuthorPosts