New (and Cheaper) HCV Therapy: Option for HIV Coinfection?

Paul E. Sax, MD


May 16, 2016

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Hi. This is Dr Paul Sax, from Brigham and Women's Hospital and Harvard Medical School. Today I'd like to discuss the January approval in the area of hepatitis C virus (HCV) treatment—the single-tablet regimen containing elbasvir and grazoprevir—and in particular, how it relates to our patients coinfected with HIV.

There are already published data in patients with coinfection. In the C-EDGE CO-INFECTION study, about 200 stable patients with HCV and HIV were given 12 weeks of this single tablet daily. Patients had genotypes 1, 4, or 6 [Editor's note: Elbasvir/grazoprevir (Zepatier™) is not approved for patients with genotype 6]. About 95% of patients achieved a cure (defined as sustained virologic response [HCV RNA < 15 IU/mL] 12 weeks after the end of therapy), with very few side effects.

Importantly, the baseline HIV regimens were limited to tenofovir/emtricitabine or abacavir and lamivudine plus one of these three active drugs: rilpivirine, raltegravir, or dolutegravir. The reason for the limitation is that there are some important drug/drug interactions with the HIV therapies—in particular, the ritonavir-boosted protease inhibitors, elvitegravir/cobicistat-containing regimens, and also efavirenz and etravirine.

Another difference between this new tablet and our other single-pill option for HCV therapy, ledipasvir/sofosbuvir, is the mechanism of action. Both combinations contain a nonstructural protein 5A (NS5A) inhibitor— ledipasvir and elbasvir are both NS5A inhibitors. The new tablet has grazoprevir, which is a hepatitis C protease inhibitor, whereas sofosbuvir is a polymerase inhibitor.

This also leads to some slight differences in pretreatment evaluation. In the package insert, it's recommended, on the basis of clinical trial data that included both HIV-positive and HIV-negative patients, that providers check their patients who have genotype 1A for the presence of certain polymorphisms that may reduce the activity of the combination. If these polymorphisms are present, then one should extend the treatment from 12 weeks to 16 weeks and also add ribavirin.

The final way that the two single tablets differ is in the price. The wholesale price that's published for grazoprevir/elbasvir is listed at about one third less than that for ledipasvir/sofosbuvir. It will be interesting to see how this plays out as the prices are negotiated with various payers.

That's a summary of the latest approved drug for HCV therapy. It's going to be sold under the brand name Zepatier™ and should be available in pharmacies very soon. Thank you very much.


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