Direct-acting antivirals
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
- ^ a b "Overview-Hepatitis C". National Health Service, UK. 21 June 2018.
- PMID 26819511.
- PMID 28319996.
- ^ "Table of Surrogate Endpoints That Were the Basis of Drug Approval or Licensure". Food and Drug Administration. 28 February 2022.
- PMC 4299677.
- .
- PMC 4530725.
- ^ 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.
- ^ .
- PMID 34636311.