The term Direct-acting antivirals (DAA) has long been associated with the combination of antiviral drugs used to treat hepatitis C infections. These are the more effective than older treatments such as ribavirin (partially indirectly acting) and interferon (indirect acting). The DAA drugs against hepatitis C are taken orally, as tablets, for 8 to 12 weeks.[1] The treatment depends on the type or types (genotypes) of hepatitis C virus that are causing the infection.[2] Both during and at the end of treatment, blood tests are used to monitor the effectiveness of the treatment and subsequent cure.[1]

The DAA combination drugs used include:[3]

  • Harvoni (sofosbuvir and ledipasvir)
  • Epclusa (sofosbuvir and velpatasvir)
  • Vosevi (sofosbuvir, velpatasvir, and voxilaprevir)
  • Zepatier (elbasvir and grazoprevir)
  • Mavyret (glecaprevir and pibrentasvir)

The United States Food and Drug Administration approved DAAs on the basis of a surrogate endpoint called sustained virological response (SVR).[4] SVR is achieved in a patient when hepatitis C virus RNA remains undetectable 12–24 weeks after treatment ends.[5][6] Whether through DAAs or older interferon-based regimens, SVR is associated with improved health outcomes and significantly decreased mortality.[7][8][9] For those who already have advanced liver disease (including hepatocellular carcinoma), however, the benefits of achieving SVR may be less pronounced, though still substantial.[9]

Despite its historical roots in hepatitis C research, the term "direct-acting antivirals" is becoming more broadly used to also include other anti-viral drugs with a direct viral target such as aciclovir (against herpes simplex virus), letermovir (against cytomegalovirus), or AZT (against human immunodeficiency virus). In this context it serves to distinguish these drugs from those with an indirect mechanism of action such as immune modulators like interferon alfa. This difference is of particular relevance for potential drug resistance mutation development.[10]

References

  1. 1 2 "Overview-Hepatitis C". National Health Service, UK. 21 June 2018.
  2. ↑ González-Grande R, Jiménez-Pérez M, González Arjona C, Mostazo Torres J (January 2016). "New approaches in the treatment of hepatitis C". World Journal of Gastroenterology. 22 (4): 1421–32. doi:10.3748/wjg.v22.i4.1421. PMC 4721977. PMID 26819511.
  3. ↑ Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB, Sulkowski MS (May 2017). "Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review". Annals of Internal Medicine. 166 (9): 637–648. doi:10.7326/M16-2575. PMC 5486987. PMID 28319996.
  4. ↑ "Table of Surrogate Endpoints That Were the Basis of Drug Approval or Licensure". Food and Drug Administration. 28 February 2022.
  5. ↑ Smith-Palmer, Jayne; Cerri, Karin; Valentine, William (December 2015). "Achieving sustained virologic response in hepatitis C: a systematic review of the clinical, economic and quality of life benefits". BMC Infectious Diseases. 15 (1). doi:10.1186/s12879-015-0748-8. PMC 4299677.
  6. ↑ Yoshida, Eric M.; Sulkowski, Mark S.; Gane, Edward J.; Herring, Robert W.; Ratziu, Vlad; Ding, Xiao; Wang, Jing; Chuang, Shu‐Min; Ma, Julie; McNally, John; Stamm, Luisa M.; Brainard, Diana M.; Symonds, William T.; McHutchison, John G.; Beavers, Kimberly L.; Jacobson, Ira M.; Reddy, K. Rajender; Lawitz, Eric (January 2015). "Concordance of sustained virological response 4, 12, and 24 weeks post‐treatment with sofosbuvir‐containing regimens for hepatitis C virus". Hepatology. 61 (1): 41–45. doi:10.1002/hep.27366.
  7. ↑ Simmons, Bryony; Saleem, Jawaad; Heath, Katherine; Cooke, Graham S.; Hill, Andrew (1 September 2015). "Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response". Clinical Infectious Diseases. 61 (5): 730–740. doi:10.1093/cid/civ396. PMC 4530725.
  8. ↑ van der Meer, Adriaan J.; Veldt, Bart J.; Feld, Jordan J.; Wedemeyer, Heiner; Dufour, Jean-François; Lammert, Frank; Duarte-Rojo, Andres; Heathcote, E. Jenny; Manns, Michael P.; Kuske, Lorenz; Zeuzem, Stefan; Hofmann, W. Peter; de Knegt, Robert J.; Hansen, Bettina E.; Janssen, Harry L. A. (26 December 2012). "Association Between Sustained Virological Response and All-Cause Mortality Among Patients With Chronic Hepatitis C and Advanced Hepatic Fibrosis". JAMA. 308 (24): 2584–2593.
  9. 1 2 Backus, Lisa I.; Belperio, Pamela S.; Shahoumian, Troy A.; Mole, Larry A. (February 2019). "Impact of Sustained Virologic Response with Direct‐Acting Antiviral Treatment on Mortality in Patients with Advanced Liver Disease". Hepatology. 69 (2): 487–497. doi:10.1002/hep.29408.
  10. ↑ Kleandrova VV, Scotti MT, Speck-Planche A (2021). "Indirect-Acting Pan-Antivirals vs. Respiratory Viruses: A Fresh Perspective on Computational Multi-Target Drug Discovery". Current Topics in Medicinal Chemistry. 21 (30): 2687–2693. doi:10.2174/1568026621666211012110819. PMID 34636311.
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