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Reuters Health Information: Oral drug combo effective for hepatitis C with HIV coinfection

Oral drug combo effective for hepatitis C with HIV coinfection

Last Updated: 2014-07-21

By Will Boggs MD

NEW YORK (Reuters Health) - The combination of two oral drugs, sofosbuvir and ribavirin, was effective for hepatitis C (HCV) infection in patients coinfected with HIV, in the open-label, nonrandomized PHOTON-1 study.

Most regimens for HCV in patients with HIV coinfection have included interferon and ribavirin along with a protease inhibitor, but these combinations are poorly tolerated, and drug interactions are problematic.

Dr. Mark S. Sulkowski from Johns Hopkins University School of Medicine, Baltimore, Maryland and colleagues analyzed sustained virologic responses (SVR) and adverse events in 223 patients with HIV and HCV genotype 1, 2, or 3 who received sofosbuvir and ribavirin.

Treatment-naïve patients with HCV genotype 2 or 3 received treatment for 12 weeks, and treatment-naïve patients with HCV genotype 1 or treatment-experienced patients with HCV genotype 2 or 3 received treatment for 24 weeks.

As reported online in the July 23/30 issue of JAMA, after two weeks of treatment, HCV RNA levels were no longer detectable in 75% of patients with HCV genotype 1, 91% of treatment-naïve patients with HCV genotype 2 or 3, and 98% of treatment-experienced patients with HCV genotype 2 or 3.

By week 4, these proportions increased to 99% in genotype 1, 99% in genotype 2 or 3, and 100% in treatment-experienced genotype 2 or 3 groups.

Three-quarters of treatment-naïve patients with HCV genotype 1 achieved SVR within 12 weeks of treatment, as did 88% of treatment-naïve patients with HCV genotype 2, 67% of treatment-naïve patients with HCV genotype 3, 92% of treatment-experienced patients with HCV genotype 2, and 94% of treatment-experienced patients with HCV genotype 3.

No one developed S282T or V321A mutations, and only four patients showed emergence of L159F mutation. None of these mutations conferred sofosbuvir resistance in vitro.

Only seven patients (3%) discontinued treatment due to an adverse event. Most adverse events were mild to moderate in severity, with fatigue, insomnia, nausea, and headache being most commonly reported.

HIV RNA levels did not change significantly in patients not receiving antiretroviral therapy at baseline, and only two patients with suppressed HIV viremia on entering the study experienced HIV viral breakthrough (one had documented nonadherence to the regimen).

"Further studies of this regimen in more diverse populations of coinfected patients are needed," the researchers add.

Dr. Michael S. Saag from the University of Alabama School of Medicine in Birmingham wrote an editorial related to this report. He told Reuters Health by email, "The standard of care is rapidly changing. Right now, the ideal should be an all oral regimen of either sofosbuvir plus ribavirin (as per the PHOTON Study) or sofosbuvir plus simeprevir. However, sometime this fall the FDA likely will approve several other oral agents: ledipisvir, daclatisvir, and three new agents from AbbVie. When this happens, it is likely that some combinations of those drugs, with or without sofosbuvir or ribavirin, will emerge as suggested regimens."

"As I point out in the editorial, we can't afford to pay for these new drugs at current pricing," Dr. Saag said. "My hope is that these newer agents will be priced substantially less than sofosbuvir and, assuming all of the regimens having (approximately) equal efficacy, allow pricing to become a major determinant of which regimen is used preferentially. My sense is that combinations of the newer agents will indeed be of similar efficacy to the currently approved direct acting agents. We will see if 'free market' forces are at play in the pharmaceutical marketplace or not."

Dr. Saag offered his view on the open-label study: "From a scientific perspective, there is no need for a comparison owing to the large amount of existing data on Peg-IFN/ribavirin regimens and its associated toxicity. From a practical perspective, patients would not sign up for such studies, and I don't blame them. The US FDA 'got this' and quite appropriately allowed a fast-track process for the development of these newer agents without requiring a randomized study vs. Peg-interferon regimens."

Dr. Raymond T. Chung from Massachusetts General Hospital in Boston, who recently reviewed the antiviral treatment of HCV, told Reuters Health by email, "Because of the very large number of patients who are ineligible for or unwilling to be treated with interferon-based regimens, the availability of an effective, well tolerated all-oral treatment will now make treatment possible. The lack of drug-drug interactions of this regimen with contemporary antiretroviral regimens will also make management of HCV in HIV coinfected persons much more straightforward than prior approved regimens."

Dr. Chung agreed with Dr. Saag about the coming new drugs, and cost issues. "We can expect even more attractive all-oral regimens in the very near future that will further enhance cure rates and shorten duration for persons with HCV infection, including those with HIV coinfection," Dr. Chung said. "We will, however, need to solve the cost problem, which threatens to limit access of these curative therapies."

Dr. Curtis Cooper from the University of Ottawa in Ontario reviewed the management of HCV/HIV coinfection in a recent issue of HIV Medicine. Now, he told Reuters Health in an email, "the paradigm in which HCV is often an after-thought for treatment in coinfection will need to be reexamined - it now makes sense to first cure HCV, thereby maximizing the safety and efficacy of HIV therapy."

Dr. Sulkowski did not respond to a request for comments.

SOURCE: http://bit.ly/1n3vX7j

JAMA 2014;312:353-361,347-348.

 
 
 
 
                 
 
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