{"id":5339,"date":"2014-07-31T17:35:14","date_gmt":"2014-07-31T21:35:14","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=5339"},"modified":"2015-06-04T14:32:14","modified_gmt":"2015-06-04T18:32:14","slug":"simeprevir-sofosbuvir-and-the-limitations-of-the-cosmos","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/simeprevir-sofosbuvir-and-the-limitations-of-the-cosmos\/2014\/07\/31\/","title":{"rendered":"Simeprevir, Sofosbuvir, and the Limitations of the COSMOS"},"content":{"rendered":"

\"the<\/a>These are exciting times for hepatitis C treatment, as the approval of simeprevir and sofosbuvir in late 2013 have made curing this disease a whole lot easier.<\/p>\n

Since that sentence barely conveys the transformative nature of this medical advance, allow me this tortured analogy: Before simeprevir and sofosbuvir, curing hepatitis C was like making a transatlantic journey by ship, and you had to stay in steerage — always a long and painful trip, but you\u2019d get there if you could stand it. Now the cure is\u00a0like a business-class flight — much shorter, safer, and more comfortable, but\u00a0you just have to have the resources to pay for it.<\/p>\n

But our treatments are not perfect. I was reminded of this fact when someone treated with simeprevir and sofosbuvir — or \u201cSIM-SOF\u201d as it’s commonly abbreviated — just relapsed a month after finishing 12 glorious, side-effect\u2013free weeks of treatment.<\/p>\n

In hindsight you could perhaps have predicted that this patient — or this type of patient — would be a\u00a0treatment failure on these new drugs. There was prior treatment failure on interferon\/ribavirin; he has genotype 1a (and hence probably Q80K, didn\u2019t test for it); he\u2019s overweight; he has several other medical problems, including diabetes.<\/p>\n

And, probably of greatest importance, he has cirrhosis, diagnosed by liver biopsy several years ago.<\/p>\n

The treatment failure sent me scurrying over to the reason we use this combination anyway — the excellent HCV treatment guidelines<\/a> and the remarkable COSMOS study<\/a> (just published in the Lancet<\/em>) of simeprevir and sofosbuvir, with and without ribavirin, in patients with HCV genotype 1.<\/p>\n

Here\u2019s what recommended in the guidelines\u00a0for patients who have failed prior treatment:<\/a><\/p>\n

Daily sofosbuvir (400 mg) plus simeprevir (150 mg), with or without weight-based RBV (1000 mg [75 kg]) for 12 weeks is recommended for retreatment of HCV genotype 1 infection, regardless of subtype or IFN eligibility.<\/p>\n

And here are the relevant data cited:<\/p>\n

Among those null responders with a Metavir fibrosis stage of 3 or 4 (n=47) who received 12 weeks of sofosbuvir and simeprevir, SVR4 was observed in 14 (93%) of 15 patients in the ribavirin-containing arm and 100% (all 7 participants) in the RBV-free arm.<\/p>\n

A few things stand out from reviewing the study and the guidelines, aside from the high response rate:<\/p>\n