Opioid Therapy No Bar to Novel HCV Drugs

MELBOURNE, Australia -- People on opioid substitution therapy for drug addiction can be safely and effectively treated for hepatitis C (HCV) with an investigational combination of medications, researchers said here.

In a small, open-label, nonrandomized trial, the interferon-free 3D combination cleared HCV in nearly 98% of patients, according to Daniel Cohen, MD, of AbbVie in North Chicago, Ill., the developer of the combination and sponsor of the study.

There were only two serious adverse events -- neither related to the study drugs -- and only one patient stopped therapy, again for a reason not associated with the medications, Cohen reported at the International AIDS Conference.

The study addresses "a very exciting and important area," commented Marion Peters, MD, of the University of California San Francisco, who was not part of the trial but who moderated the session at which it was presented.

She noted that many injection drug users need opioid substitution therapy and many also have HCV, but have not been candidates for treatment, except in very specialized centers.

That's because HCV therapy, until recently, was based on injections of pegylated interferon-alfa, which "messes with the head, it's such a toxic drug," Peters told MedPage Today.

"So this is really exciting data that you can now use all-oral medications," she said.

It's especially important, she said, to know that the 3D combination does not interfere with drugs used for opioid substitution -- in this study, either methadone or buprenorphine, with or without naloxone.

The 3D combination includes three "direct-acting agents," or DAAs, that target different aspects of HCV replication. It's one of a wave of new drugs and drug combinations, some approved and some still experimental, aimed at curing the virus.

Until recently, the combination was known by a soup of numbers and letters, because the drugs involved had yet to be named. But ABT-267, an NS5A inhibitor, is now ombitasvir and the non-nucleoside polymerase inhibitor ABT-333 is now called dasabuvir. The still-nameless third drug is ABT-450, a protease inhibitor boosted with ritonavir (Norvir).

The combination is given with ribavirin, a nonspecific drug that modifies host factors in viral infections.

The drug has been tested in more than 2,700 people, Cohen noted, but none of them has been on opioid substitution. To help fill the gap, Cohen and colleagues enrolled 38 HCV patients taking either methadone or buprenorphine.

While many such patients also have HIV, co-infected patients were not included in this trial, he said. Other studies have shown that HCV-HIV co-infected patients do well on the 3D combination, however.

Patients, all with chronic genotype 1 HCV, were treated for 12 weeks, and the primary endpoint was the proportion who had undetectable virus 12 weeks after the end of therapy -- the so-called SVR₁₂, which is regarded as a cure.

Of the 38 patients, 37 (97.4%) achieved an SVR₁₂, Cohen said.

One patient stopped therapy early after suffering a stroke, Cohen said, but it was not thought to be related to the study drugs. Another patient developed myeloid leukemia during the trial, but completed the study and reached SVR₁₂.

Most patients reported at least one treatment-emergent adverse event, but they were mainly mild nausea, fatigue, and headache.

Seven patients reduced the dose of ribavirin during therapy owing to reduced hemoglobin or anemia -- a known effect of ribavirin -- but the change did not affect treatment success.

Indeed, Cohen noted, the recently reported PEARL studies showed that ribavirin can be dropped entirely without affecting treatment success rates, but that data wasn't available when this trial was designed.

Importantly, none of the patients needed to change the dosage of methadone or buprenorphine, Cohen said.

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