Successful 8-week treatment of newly diagnosed HCV genotype 1 adds to evidence that early detection could enable shorter, less costly treatments.
Marianne Martinello, MBBS, PhD
Successful treatment of recently acquired hepatitis C virus (HCV) genotype 1 infection in 8 weeks, with a regimen currently approved for 12 weeks, adds to growing evidence that early detection could enable shorter, less costly treatment and more rapid reduction of the infectious viral pool.
Marianne Martinello, MBBS, PhD, of the Viral Hepatitis Clinical Research Program, Kirby Institute, University of New South Wales, Australia, and colleagues contributed a new study to the list of trials involving shortened durations of direct-acting antiviral (DAA) regimens for acute and recent HCV infections.
Their new findings suggest early detection is key to more patients being eligible for these increasing, and increasingly efficient treatment options.
"This initial assessment represents an ideal opportunity for intervention, with benefits at both an individual level and the population level, largely related to averting onward transmission," Martinello and colleagues wrote. "Cost-effectiveness analysis supports immediate treatment of acute HCV with short-duration DAA therapy as compared with treatment deferral until chronic infection, given cost savings associated with shorter treatment duration and reduced transmission."
The investigators examined whether an 8-week regimen of paritaprevir/ritonavir/obmitasvir (P/R/O) and dasabuvir (Viekira) could achieve the same clinical goal of sustained virologic response (SVR) at 12 weeks in DAA-treatment naive patients with recent HCV genotype (GT) 1 infection without cirrhosis that is associated with a 12-week course of treatment. Weight-based ribavirin was added in those with GT 1a and GT 1, no subtype.
Subjects with HIV co-infection were included if their antitretroviral therapy was stable for at least 8 weeks prior to screening, their CD4 count was >200 cells/mm3, and their plasma HIV RNA was undetectable.
Thirty subjects were identified with an HCV GT1 infection of less than 12 months at screening, with the date of infection estimated as 6 weeks before the onset of seroconversion illness or before the first alanine aminotransferase (ALT) greater than 10 times the upper limit of normal. HIV co-infection was documented in 23 individuals, and 7 required alterations in their antiretroviral (ART) regimen to avoid potential drug-drug interactions. One subject withdrew from the study after 2 weeks of treatment due to hospitalization for an unrelated adverse event.
Martinello and colleagues reported that 100% of the remaining 29 patients completed the 8 weeks of treatment, and that all achieved SVR at the 12-week measure. Their adherence to treatment was assessed by pill count and self-reported adherence questionnaires at treatment weeks 2, 4, 6, and at the end of treatment on week 8.
The median time to attain HCV RNA below the lowest limit of quantification (10IU/ml) and to undetectable was 14 days (range 13 - 42) and 28 days (range 14 - 140), respectively. ALT levels also rapidly declined, with median ALT levels at baseline, week 2 and end of treatment at week 8 of 152, 34, and 21 U/L, respectively.
The investigators noted that SVR12 was attained regardless of some subjects having a high baseline HCV RNA. In addition, 2 subjects were found by pill count to have had less than 90% adherence to the regimen. One subject had 70% adherence to the P/R/O, 85% adherence to dasabuvir and 100% adherence (at week 4) to ribavirin; the other was 91% adherent to the P/R/O, 82% adherent to dasabuvir and 77% adherent to ribavirin.
The investigators described other studies of shortened treatments in acute and recent HCV infection, including pilot studies of dual- and triple-class DAA regimens for 4, 6 and 8 weeks. Among the promising studies are trials with sofosbuvir/ledipasvir (Harvoni) conducted in patients with HIV co-infection for 6 and 8 weeks, and for 4 and 6 weeks in patients with HCV GT1 mono-infection.
"Combined, these studies offer exciting potential, suggesting that, as with interferon-based therapy, DAA treatment duration may be reduced in recent as compared with chronic HCV infection," Martinello and colleagues concluded.
The study, "Shortened therapy of eight weeks with paritaprevir/ritonavir/ombitasvir and dasabuvir is highly effective in people with recent HCV genotype 1 infection," was published online in the Journal of Viral Hepatitis.