A dual combination of Merck's grazoprevir and elbasvir taken for 12 or 16 weeks cured most HIV-positive people with genotype 1, 4 or 6 hepatitis C virus (HCV) co-infection 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, USA.
Grazoprevir (an HCV NS3/4 protease inhibitor) and elbasvir (a NS5A inhibitor) are being studied as a once-daily single-tablet regimen for chronic hepatitis C. Both drugs have demonstrated activity against multiple HCV genotypes. The combination is currently under review by the US Food and Drug Administration (FDA).
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 and HCV co-infection (C-EDGE Co-infected) and people with advanced liver disease (C-SALT) or chronic kidney disease (C-SURFER).
At IDWeek, Mark Nelson of Chelsea and Westminster Hospital in London presented findings from an integrated analysis of all people with HIV and HCV co-infection enrolled in phase 2 and 3 trials of grazoprevir/elbasvir. Phase 2 studies tested grazoprevir and elbasvir as separate drugs, while phase 3 trials evaluated the co-formulation.
A total of 298 people with HIV and HCV genotypes 1, 4 or 6 comprised 19% of the phase 2/3 study population (31% of treatment-naive participants and 3% of those previously treated with pegylated interferon and ribavirin):
- C-WORTHY: 59 people with HIV and HCV co-infection (15% of study population)
- C-EDGE Co-infected: 218 people, all with HIV and HCV co-infection
- C-EDGE Treatment-experienced: 21 people with HIV and HCV co-infection (9% of study population)
About 85% of participants with co-infection were men (compared with about 60% of participants with HCV mono-infection), 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 one person had genotype 6. More than 90% were previously untreated; 13% of treatment-naive and 24% of treatment-experienced participants had liver cirrhosis.
Participants could either be on stable, suppressive antiretroviral therapy (ART) using tenofovir/emtricitabine (Truvada) or abacavir/lamivudine (Kivexa or Epzicom) plus raltegravir (Isentress), dolutegravir (Tivicay) or rilpivirine (Edurant); or else had a CD4 cell count above 500 cells/mm3 and had not yet started ART.
All 277 treatment-naive participants with HIV and HCV co-infection were treated with grazoprevir/elbasvir (100mg/50mg) for 12 weeks; 29 also took ribavirin while 248 did not. The 21 treatment-experienced participants with co-infection received grazoprevir/elbasvir for 12 or 16 weeks (about half each); nine people added ribavirin while 12 did not.
Within the treatment-naive group, overall efficacy was comparable between people with HIV and HCV co-infection and people with HCV mono-infection, with 94% achieving sustained virological response, or continued undetectable HCV RNA 12 weeks after completing treatment (SVR12). Treatment-naïve participants with co-infection 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 people with co-infection receiving grazoprevir/elbasvir with 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 study arm were small).
Efficacy was similar regardless of cirrhosis status in both the treatment-naive and treatment-experienced groups.
Ten treatment-naive and one treatment-experienced participant with co-infection experienced virological failure, primarily relapse, while six people had treatment failure for other reasons.
Grazoprevir/elbasvir was generally safe and well-tolerated for people with co-infection, with no drug-related serious adverse events or discontinuations due to adverse events. The frequency and duration of side-effects were comparable between participants with HIV and HCV co-infection and those with HCV mono-infection. No participants with co-infection required a change in ART regimen during treatment with grazoprevir/elbasvir.
"High rates of SVR were achieved in patients with HIV/HCV co-infection," 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] co-infection."
Nelson M et al. High efficacy of grazoprevir/elbasvir among HCV GT1, GT4, or GT6 infected patients with HIV co-infection. IDWeek 2015, abstract 1267, 2015.