title: Chronic hepatitis C genotype 1 treatment roadmap for resource constrained settings.
abstract: OBJECTIVE
  To use existing hepatitis C virus (HCV) antiviral therapies as access to new treatments is limited.
  
  
  METHODS
  A PubMed search for randomised control trials or meta-analysis related to response-guided therapy of HCV genotype 1 patients was undertaken using pegylated interferon and ribavirin (PR), boceprevir (B) and telaprevir (T) and lead-in where response-guided therapy at TW4(TW4), 8(TW8), 10(TW10), or 12(TW12) based on HCVRNA(+) or HCVRNA(-). Studies presented at major conferences were also used. Where necessary, a post-hoc analysis was performed. A response-guided management roadmap was created based on sustained virological response (SVR).
  
  
  RESULTS
  Starting with PR, those with HCVRNA(-) at TW4 have > 86% SVR, while those are HCVRNA(+) have 34%-41.7% SVR. HCVRNA(-) TW4 patients can have 24 wk PR if HCVRNA < 400000 IU/mL. Alternatively, 28 wk BPR has similar SVR. If HCVRNA(+) at TW4, 72 wk PR leads to 53% SVR, hence BPR is a better option, and if HCVRNA(-) by TW8, 28 wk therapy is sufficient. If HCVRNA(+) at TW8, then HCVRNA should be checked at TW10 and TW12. By TW12, HCVRNA ≥ 100 IU/mL activates the stopping rule. This roadmap is applicable for treatment-naïve, treatment failures and cirrhotic patients. Validation from an Asia Pacific early access boceprevir program confirmed the findings that HCVRNA(-) at TW4, or TW8 conferred > 80% SVR, leading to the "80-80" rule.
  
  
  CONCLUSIONS
  Using a roadmap based on HCVRNA(-) at TW4 or TW8 (the "80-80" rule), high SVR can be achieved, and guide the best choices for treatment, and also reduces drug exposure in poor responders.
authors: Seng Gee Lim, Department of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
authors: Seng Gee
authors: SG
authors: Lim
mesh_terms: D000998:Antiviral Agents / Q000191:economics / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D019091:Critical Pathways; D003695:Delivery of Health Care / Q000191:economics; D003906:Developing Countries / Q000191:economics; D016527:Drug Costs; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics; D006801:Humans; D018579:Patient Selection; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D012367:RNA, Viral
keywords: Boceprevir; Chronic hepatitis C; Cirrhosis; Partial responder; Peginterferon; Response-guided therapy; Ribavirin; Sustained virological response; Telaprevir; hepatitis C virus RNA