It is lovely to see people who missed out first time round not draw a short straw the second time.

Most people succeed first time.

Sadly a few don’t but as we can see here, and elsewhere, yes it’s a setback, but SVR is still out there and we just have to work a little harder to get there.

Triple drug therapy with an NS3/4A, NS5A and NS5B is the way to go if you can get it.

Adding generic Sofosbuvir to Viekira and Zepatier is the simplest solution where these are available.

Relatively affordable Abbvie Viekira can be sourced out of Egypt if required.

Extended treatment with Sof+Vel+Ribavirin is probably the next best option, but it needs to be done on a case by case basis.

Hello Meri,

There are 5 basic causes of dyspnoea

1. Respiratory
2. Cardiac
3. Blood
4. Musculoskelatal
5. Neurological

We need to look at all these in turn to find the cause, starting with the most likely.

With the lungs Xray, spirometry (pre and post bronchodilator) and a CT chest would be the starting point.

For the heart and ECG will show rhythm problems and old heart attacks, enzymes are useless in this context as they are only elevated when you have a heart attack for a maximum of 1 week. We do see them elevated with myocarditis (infection/inflammation of the heart) but this is rare. What you need is an echocardiogram (Ultrasound of the heart) to assess valve and muscle function as well as pulmonary pressures.

A full blood count will show anaemia and other blood cell problems. The CMP will look at liver and kidneys.

Musculoskeletal problems are assessed clinically

Neurological things are rare and last on the list.

Here is what the Mayo Clinic has to say about it: http://www.mayoclinic.org/symptoms/shortness-of-breath/basics/definition/sym-20050890

Hi RSF,

Hopefully it’s not, but if it is we will just have to fix it won’t we?

Another way of looking at it is like this.

The WHO estimate has dropped to 70 million with HCV.

Currently, we treat 17 million patients with HIV with 52 weeks of double, triple or quadruple antivirals.

These antivirals are similar to HCV antivirals.

So 17 million full year treatments are the same as 17*52/12 = 73.6 million 12 week treatments.

In short we have proven capacity to make enough antiviral medicine for every patient in the world with HCV in a single year. We already produce more than this quantity for HIV.

It took us 10 years to get to that scale, but still, it is quite clearly doable without raising much of an industrial sweat.

That’s fabulous news Coral

Hello 2b,

While there is no good guidance on this, in mg/kg terms you are getting the same dose as somebody of about 70kg. We don’t consider dose increases for 80, 90, 100, 100 kg patients so if things seem better on this slightly reduced dose I think it should not impact treatment success.

As an experiment, if you take the full tablet for a day or two and the problems recur that would be compelling evidence we are giving you just a little too much.

Hello Gert,

Yes, there are studies. You want page 18 of the EASL Guidelines (see PDF) that reports the major studies used for the guidelines and provides references for them you can then look up.

SOF+VEL: ASTRAL-3

Short version: http://slides.hcvonline.org/uploads/194/astral3.pdf
Long version: http://www.nejm.org/doi/full/10.1056/NEJMoa1512612#t=article

SOF+DCV: ALLY-3 and ALLY-3+

Short version: http://slides.hcvonline.org/uploads/164/ally3.pdf
Long vesion: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409820/

ALLY-3+ https://www.ncbi.nlm.nih.gov/pubmed/26822022

There is another bigger SOF+DCV trial here: http://fixhepc.com/forum/gt3/369-gt3-high-svr-rates-with-daclatasvir.html which includes a PDF of the results. It does not have a funky name AFIK.

You may notice that the results for SOF+DCV vary a bit and include similar optimistic numbers to SOF+VEL

Now this table is interesting (and you won’t easily find it). It comes from Abbvie who were talking about how good G/P is (previously called ABT-493/ABT-530). GS-9857 is Voxilaprevir in case you’re wondering.

In theory Velpatasvir should be better – It has an EC50 of 20 vs 530 for daclatasvir, but only about 25% gets absorbed so that robs it of part of the 26.5x theoretical edge, dropping it to say 7x, but then the dose is 100 mg vs 60 mg so that pushes it up to about 10x.

Now resistance comes in 10x, 100x and 1000x strengths so 10x is just enough to probably make a real difference for a few patients.

I have no doubt that 16 weeks SOF+DCV works better in GT3 patients than 12 weeks, so that is a factor.