December 8, 2013
We have been here before: A new, deadly virus is found to be spreading; treatments are developed, but are toxic, plus they have limited efficacy; and then, all of a sudden, there is a breakthrough and potent therapies spill onto the market, offering hope for millions. There are few events in medical history that can rival the advent of combination antiretroviral therapy, but the coming direct-acting therapies for hepatitis C virus (HCV) infection are nothing short of mind-blowing.
This year, we saw the first studies of these new drugs in HIV-HCV coinfected individuals. The NS5B polymerase inhibitor sofosbuvir was shown to be effective when added to 12 weeks of interferon and ribavirin (IFN/RBV) in coinfected patients in a small study in which 91% achieved a sustained virologic response (SVR) at week 12 post therapy. Even more exciting were the results from the PHOTON-1 trial in which coinfected patients received sofosbuvir and ribavirin alone for 24 weeks if the virus was genotype 1 (N = 114) or 12 weeks if it was genotype 2 or 3 (N = 109 combined). Genotype 1 harboring patients had a 12-week SVR of 76% (88% for genotype 2 and 67% for genotype 3).
Simeprevir, an NS3/4A protease inhibitor, also proved itself in coinfected patients, with an SVR of 74% when co-administered with IFN/RBV in a study of 106 patients with genotype 1 virus. The SVR rate was slightly higher for those who were HCV treatment naive and those with subtype 1b were more likely to achieve an SVR than those with 1a (89% versus 71%). A lower rate (67%) of SVR was observed for patients with 1a subtype and the Q80K NS3 resistance mutation detected at baseline.
The response of coinfected patients to sofosbuvir and simeprevir, as well as a number of other direct-acting HCV antivirals in development, has exceeded expectations and there is an obvious giddiness in treaters anticipating all the cures to be had in 2014. The promise of interferon-sparing regimens only amps up this euphoria.
We and our patients have waited a long time for a HAART-like advance in HCV treatment and now it is at hand. It remains to be seen how accessible these new drugs will be for those with coinfection. Although, that HIV-infected patients have been able to receive boceprevir and telaprevir, is encouraging.
The new HCV treatments also will have other collateral benefits. The management of HIV has frankly become somewhat rote. There certainly remain important challenges, including maintaining engagement of patients in care, dealing with ample mental health and substance abuse co-morbidities, and addressing diseases of aging in those living with HIV. However, as mentioned below, the vast majority of patients under care are doing well and clinic visits for many patients have been reduced to pleasantries, a cursory examination, and then a shuffle off to the lab for blood work that will not reveal detectable virus. We worked hard to get to this level of monotony and it is welcome.
HCV management now offers many of us a jolt. We entered this field to make a difference -- perhaps even to rid people of their infections -- and with these new agents we can. Being in the cure business is good for our patients and for us.
So, what can go wrong? How about pricing that makes your head spin: over $60,000 for a 12-week course of simeprevir, which seems like a bargain when held up against the $84,000 price tag of a similar course of sofosbuvir. Gilead, the maker of sofosbuvir, has apparently agreed to create a generous patient support program at the urging of the Fair Pricing Coalition, but one wonders whether these "concessions" actually enabled the company to arrive at this stratospheric price. Clearly, pharmaceutical companies make huge investments in developing novel medications and their gambles often do not pay off. However, one wonders how many people who were not able to be cured of HCV when therapy was less effective but affordable will now not be cured because therapy is effective but unaffordable.
What are some other top clinical developments of 2013? Read more of Dr. Wohl's picks.
David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina and site leader of the University of North Carolina AIDS Clinical Trials Unit at Chapel Hill.