HCV Antivirals Produce Durable Responses Despite Time to Suppression

Sustained virologic response seen for newer combinations of HCV genotype 1b antivirals. <i>Photo Credit: Prof. François Potet / CNRI / Science Source.</i>
Sustained virologic response seen for newer combinations of HCV genotype 1b antivirals. Photo Credit: Prof. François Potet / CNRI / Science Source.

Sustained response to newer combinations of antiviral agents used to treat hepatitis C virus (HCV) was achieved despite a longer time to viral suppression in adults with chronic genotype 1b (GT1b) forms of the disease, reported the investigators of a multinational study published recently in the Journal of Viral Hepatitis.1

The results of 6 phase 3 clinical trials (SAPPHIRE I & II, PEARL II-IV, and TURQUOISE I & II) of the novel combinations of ombitsavir (OBV), paritaprevir with ritonavir (PTV/r), and dasabuvir (DSB) with or without ribavirin (RBV) all demonstrated suppression rates of 95% to 100% at 12 weeks in patients with HCV GT1 subtype.2-6 

The investigators in the current study, led by Saleh Ali Alqahtani, MBBS, medical director of International Digestive & Liver Services at Johns Hopkins University Medical Center in Baltimore, Maryland, conducted a pooled analysis of 2027 patients from these 6 trials to evaluate the potential impact of differences in the times to initial virologic response on sustained virologic response (SVR) among the cohort. Patients began to respond to therapy early in the trials, with initial suppression measured by lower limit of quantification assay (LLOQ = 25 IU/mL) at weeks 1 (31%), 2 (81%), 4 (99%), and 6 (100%).

Certain factors, including older age, a diagnosis of cirrhosis, a higher baseline level of HCV, and a lack of response to previous pegylated interferon therapy, all contributed to a slower response. The investigators were surprised to identify a subgroup of HCV GT1b patients as slow responders, of whom more than 80% had an initial response later than 2 weeks, although they concluded that this difference was not substantial enough to impede SVR to therapy at 12 weeks.

“Persons infected with HCV genotype 1b are more responsive to HCV treatment with this regimen,” explained Mark Sulkowski, MD, medical director of the Viral Hepatitis Center at Johns Hopkins University Medical Center and another of the study investigators. “In the study by Ferenci et al (New Engl J Med, 2014),4 the 3-drug regimen — paritaprevir/r/ombitasvir + dasabuvir — led to a 99% SVR rate in persons with HCV genotype 1b infection with or without the addition of ribavirin; on the other hand, persons with HCV genotype 1a infection had a 90% SVR rate with the 3-drug regimen without ribavirin, and when ribavirin was added this increased to 97%. The consensus concept is that with this regimen, HCV genotype 1b infection is highly responsive and treatment failure rarely reported; in this context, the initial slower HCV RNA response was unexpected.”

The findings from this study further support evidence from 6 previous clinical trials that an interferon-free treatment regimen of OBT/PTV/r plus DSV achieves rapid virologic response by week 4 that is sustained to week 12.

References

  1. Alqahtani S, Ozaras R, Isakov V, et al. Time to viral suppression is not related to achievement of SVR12 in HCV GT1-infected patients treated with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin [published online December 9, 2016]. J Viral Hepat. doi: 10.1111/jvh.12641
  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;147:359-365. e1. doi: 10.1053/j.gastro.2014.04.045
  3. Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1594-1603. doi: 10.1056/NEJMoa1315722
  4. 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. doi: 10.1056/NEJMoa1402338
  5. Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014;370:1973-1982. doi: 10.1056/NEJMoa1402869
  6. Zeuzem S, Jacobson IM, Baykal T, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1604-1614. doi: 10.1056/NEJMoa1401561
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