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SVR12 Rate 97% With 3 DAAs Plus Ribavirin in People on Opioid Replacement
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20th International AIDS Conference, July 20-25, 2014, Melbourne
Mark Mascolini
Thirty-seven of 38 HCV-1-infected people on stable opioid replacement therapy attained sustained virologic response 12 weeks after therapy ended (SVR12) with three direct-acting antivirals (DAAs, ABT-450/ritonavir, ombitasvir, and dasabuvir) plus ribavirin [1]. The findings demonstrate that interferon-free regimens can yield high response rates even in challenging populations like recovering drug users who are opoid replacement therapy.
ABT-450 is a ritonavir-boosted HCV NS3/4A protease inhibitor, ombitasvir inhibits the HCV NS5A replication complex, and dasabuvir is a nonnucleoside NS5B polymerase inhibitor. Ombitasvir/ABT-450/r + Dasabuvir Phase 3 Results - The 3D regimen been studied in >2700 patients to date; 12 weeks of 3D + RBV resulted in SVR12 in 96% of treatment-naïve and experienced GT1-infected patients without cirrhosis; 12 weeks of 3D without RBV resulted in SVR12 in 99%-100% of treatment-naïve and treatment-experienced GT1b-infected patients without cirrhosis. In phase 3 trials of these three DAAs, the overall discontinuation rate is 2%. Coformulated ABT-450/r/ombitasvir, now in regulatory review, was used in this trial [1].
Because interferon-based regimens pose steep challenges to people who inject drugs, including those on opioid-replacement therapy, researchers conducted this phase 2 open-label trial at 8 sites in North America. All participants had chronic HCV type 1 infection, and none had cirrhosis. All were HCV treatment-naive or had taken only pegylated interferon/ribavirin, and all were receiving stable opioid replacement therapy with methadone or buprenorphine (with or without naloxone). No one had evidence of HBV coinfection, and none had liver disease other than HCV infection. For 12 weeks study participants took coformulated ABT-450/r/ombitasvir (two tablets once daily), dasabuvir (one tablet twice daily), and weight-based ribavirin.
Of the 38 the study participants, 19 were taking methadone and 19 buprenorphine. Two thirds were men, 95% were white, 95% were naive to HCV therapy, two thirds had genotype 1a infection, and two thirds had an IL28b non-CC genotype. (People with a CC genotype have a stronger immune response to HCV infection than people with a CT or TT genotype). The study group averaged 48.2 years in age, and 79% had F0-F1 fibrosis.
One study participant stopped treatment early because of serious adverse events not related to study drugs (cerebrovascular accident and sarcoma). The 37 remaining patients (97.4% of 38) all attained an end-of-treatment response, SVR4, SVR12, and SVR24. No study participants had virologic failure.
Two people (5.3%) had a severe adverse event, 2 had a serious adverse event (both unrelated to study drugs), and 35 (92%) had any adverse event. The most common adverse events were nausea (in 50%), fatigue (in 47.4%), and headache (in 31.6%). Hemoglobin fell below 10 g/dL in 8 study participants (21%) during treatment. Seven of these 8 lowered their ribavirin dose and all achieved SVR24. No dose adjustments were needed for methadone or buprenorphine.
The researchers noted that SVRs attained in this population are comparable to prior results in treatment-naive and experienced people with genotype 1 HCV. They suggested this 12-week regimen "may be an attractive treatment option for GT1-infected patients receiving opioid replacement therapy."
References
1. Lalezari J, Sullivan JG, Varunok P, et al. Interferon-free 3 DAA plus ribavirin regimen in HCV genotype 1-infected patients on methadone or buprenorphine. AIDS 2014. 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract MOAB0103.
2. Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014 pii: S0016-5085(14)00603-9.
3. Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370:1983-1992.
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Interferon-free 3 DAA Plus Ribavirin Regimen in HCV Genotype 1-Infected Patients on Methadone or Buprenorphine
Reported by Jules Levin
20th International AIDS Conference, Melbourne, Australia, 21 July 2014
Jacob Lalezari, J Greg Sullivan, Peter Varunok, Edward Galen, Kris V Kowdley, Vinod Rustgi, Humberto Aguilar, Franco Felizarta, Martin King, Daniel Cohen
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