IDWeek 2015: HIV/HCV Coinfected People Achieve High Cure Rates with Grazoprevir/Elbasvir

A dual combination of Merck's grazoprevir and elbasvir taken for 12 or 16 weeks cured most HIV-positive people coinfected with hepatitis C virus (HCV) genotypes 1, 4, or 6, and was generally safe and well-tolerated, according to an integrated analysis of three trials presented at the recent IDWeek 2015 conference in San Diego.

Grazoprevir (an HCV NS3/4 protease inhibitor) and elbasvir (a NS5A inhibitor) are being studied as a once-daily single-tablet regimen. Both drugs have demonstrated activity against multiple HCV genotypes. The combination is currently under review by the U.S. Food and Drug Administration

Studies presented at this year's EASL International Liver Congress showed cure rates of 90% or higher for previously untreated people (C-EDGE treatment-naive), prior non-responders to interferon-based therapy (C-EDGE treatment-experienced), those unsuccessfully treated with a first-generation HCV protease inhibitor (C-SALVAGE), people with HIV/HCV coinfection (C-EDGE coinfected), and patients with advanced liver disease (C-SALT) or chronic kidney disease (C-SURFER).

At IDWeek Mark Nelson from Chelsea and Westminster Hospital in London presented findings from an integrated analysis of all people with HIV/HCV coinfection enrolled in Phase 2/3 trials of grazoprevir/elbasvir; Phase 2 studies tested grazoprevir and elbasvir as separate drugs, while Phase 3 trials evaluated the coformulation.

A total of 298 coinfected patients with HCV genotypes 1, 4, or 6 comprised 19% of the Phase 2/3 study population (31% of treatment-naive patients and 3% of those previously treated with pegylated interferon and ribavirin):

• C-WORTHY: 59 coinfected patients (15% of study population);
• C-EDGE Co-infected: 218 patients, all coinfected;
• C-EDGE Treatment-experienced: 21 coinfected patients (9% of study population).

About 85% of coinfected participants were men (compared with about 60% of monoinfected patients), with a mean age of approximately 50 years. About 65% had hard-to-treat HCV genotype 1a, about 22% had 1b, 12% had genotype 4, and 1 person had genotype 6. More than 90% were previously untreated; 13% of treatment-naive and 24% of treatment-experienced patients had liver cirrhosis.

Participants could either be on stable, suppressive antiretroviral therapy (ART) using tenofovir/emtricitabine (Truvada) or abacavir/lamivudine (Epzicom) plus raltegravir (Isentress), dolutegravir (Tivicay), or rilpivirine (Edurant); or else had a CD4 T-cell count above 500 cells/mm³ and had not yet started ART.

All 277 treatment-naive coinfected participants were treated with grazoprevir/elbasvir (100mg/50mg) for 12 weeks; 29 also took ribavirin while 248 did not. The 21 treatment-experienced coinfected patients received grazoprevir/elbasvir for 12 or 16 weeks (about half each); 9 added ribavirin while 12 did not.

Results

• Within the treatment-naive group, overall efficacy was comparable between HIV/HCV coinfected and HCV monoinfected patients, with 94% achieving sustained virological response, or continued undetectable HCV RNA 12 weeks after completing treatment (SVR12).
• Treatment-naive coinfected participants had similar response rates using ribavirin-free and ribavirin-containing regimens (94% vs 97%, respectively).
• Within the treatment-experienced group, SVR12 rates were 100% for coinfected patients receiving grazoprevir/elbasvir without or without ribavirin for 12 weeks, 83% for those treated without ribavirin for 16 weeks, and 100% for those treated with ribavirin for 16 weeks (numbers in each arm were small).
• Efficacy was similar regardless of cirrhosis status in both the treatment-naive and treatment-experienced groups.
• 10 treatment-naive and 1 treatment-experienced coinfected patients experienced virological failure, primarily relapse, while 6 people had treatment failure for other reasons.
• Grazoprevir/elbasvir was generally safe and well-tolerated for coinfected patients, with no drug-related serious adverse events or discontinuations due to adverse events.
• The frequency and duration of adverse events were comparable between HIV/HCV coinfected and HCV monoinfected participants.
• No coinfected patient required a change in ART regimen during treatment with grazoprevir/elbasvir.

"High rates of SVR were achieved in patients with HIV/HCV coinfection," the researchers concluded. "With low rates of adverse events, once-daily administration, and suitability for use in patients also receiving antiretroviral therapy, grazoprevir/elbasvir represents a highly effective treatment option for patients with [HIV/HCV] coinfection."

11/11/15

Reference

M Nelson, J Rockstroh, J Mallolas, et al. High Efficacy of Grazoprevir/Elbasvir Among HCV GT1, GT4, Or GT6 Infected Patients with HIV Co-Infection. IDWeek 2015. San Diego, October 7-11, 2015. Abstract 1267.