Are There Remaining Challenges in Hepatitis C Therapy?

Prompted by (yet more) spectacular HCV study results, I posted the following questions on Twitter:

Is velpatasvir/sofosbuvir the endgame for HCV? And what will HCV researchers do now? @NEJM

-- Paul Sax (@PaulSaxMD) November 18, 2015

To which I got this reply from one of our very energetic second-year ID fellows:

@PaulSaxMD @NEJM what about coinfected patients, drug interactions?

-- Philip Lederer (@philiplederer) November 18, 2015

OK, OK, I know what you're wondering -- don't you two have anything better to do than fool around with a financially struggling social media platform?

Sure we do -- but after years and years of "not getting" Twitter, I now (thanks to Phil) see some of the benefits, namely the rapid exchange of information and ideas, in a particularly efficient form.

But back to the topic at hand, which is the HCV regimen used in these latest studies published in the New England Journal of Medicine. All include the pan-genotypic NS5A inhibitor velpatasvir with the already-approved nucleotide sofosbuvir, given as a single pill once daily.

Results? Outstanding:


The results really make you wonder what more we can do to make HCV treatment better. We are definitely at the flat part of the response curve, and fortunately it has plateaued way up there, with 95% or higher cure rates for all but the sickest HCV patients, along with exceedingly rare adverse effects.

So are there remaining issues? Yes, sort of -- but none of them is as pressing as the obligatory elephants in the room, which are cost and access. Let's start with Phil's proposed challenges, plus a few others:

  • Co-infected patients. Not really a problem at all -- people with HIV respond just as well as those without coinfection. (Several examples of studies cited in this post.) In fact, in many ways they've been easier to treat, as the patients are already used to taking medications every day.
  • Drug-drug interactions. Compared to what we've dealt with using ritonavir and cobicistat and rifampin, these are a piece of cake -- unless you're actually using ritonavir with the "PrOD" regimen. (That's what I've been calling it. I never liked "3D".)
  • Cirrhosis. Especially with a history of treatment failure to interferon-based therapies. In most studies, the newer drugs don't work quite as well in these patients -- but we're generally talking small differences. Response rates are still pretty great.
  • Patients who have failed treatment an NS5A inhibitor-containing regimen. Indeed, this does limit our options quite a bit, and assessing for resistance is anything but straightforward, especially with non genotype 1. But we're not completely without options -- alternative sofosbuvir-based regimens will work in some patients, as the resistance barrier to this particular drug is sky high. I suspect we'll get some clarity on this issue over the next several months.
  • Patients who can't take 12 weeks of therapy. Most studies of treatment for less than 12 weeks have been disappointing. Does a shorter course mean better adherence? Lower cost? Better outcomes? Maybe. Hard to beat the current rate of cure, but still -- a regimen that could be given for 2-4 weeks would be welcome for some patients. Think H pylori treatment, if you can stand the analogy, since ID doctors know squat about H pylori therapy.
  • Cost. See elephants in the room, cited above. Maybe the soon-to-be-approved grazoprevir/elbasvir. We'll see.

So what about the second part of that tweet?

And what will HCV researchers do now?

I don't know -- become experts in implementation research? Switch to steatohepatitis? Study how to cure hepatitis B? Learn how to juggle clubs?

Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.