Your browser doesn't support javascript.
loading
Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study.
Flower, Barnaby; Hung, Le Manh; Mccabe, Leanne; Ansari, M Azim; Le Ngoc, Chau; Vo Thi, Thu; Vu Thi Kim, Hang; Nguyen Thi Ngoc, Phuong; Phuong, Le Thanh; Quang, Vo Minh; Dang Trong, Thuan; Le Thi, Thao; Nguyen Bao, Tran; Kingsley, Cherry; Smith, David; Hoglund, Richard M; Tarning, Joel; Kestelyn, Evelyne; Pett, Sarah L; van Doorn, Rogier; Van Nuil, Jennifer Ilo; Turner, Hugo; Thwaites, Guy E; Barnes, Eleanor; Rahman, Motiur; Walker, Ann Sarah; Day, Jeremy N; Chau, Nguyen V V; Cooke, Graham S.
Afiliación
  • Flower B; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Hung LM; Department of Infectious Disease, Imperial College London, London, United Kingdom.
  • Mccabe L; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Ansari MA; MRC Clinical Trials Unit at UCL, University College London, London, United Kingdom.
  • Le Ngoc C; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Vo Thi T; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Vu Thi Kim H; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Nguyen Thi Ngoc P; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Phuong LT; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Quang VM; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Dang Trong T; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Le Thi T; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Nguyen Bao T; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Kingsley C; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Smith D; Department of Infectious Disease, Imperial College London, London, United Kingdom.
  • Hoglund RM; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Tarning J; Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Faculty of Tropical Medicine, Bangkok, Thailand.
  • Kestelyn E; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.
  • Pett SL; Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Faculty of Tropical Medicine, Bangkok, Thailand.
  • van Doorn R; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.
  • Van Nuil JI; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Turner H; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.
  • Thwaites GE; MRC Clinical Trials Unit at UCL, University College London, London, United Kingdom.
  • Barnes E; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.
  • Rahman M; Oxford University Clinical Research Unit, Hanoi, Vietnam.
  • Walker AS; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Day JN; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.
  • Chau NVV; MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom.
  • Cooke GS; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Elife ; 122023 Jan 09.
Article en En | MEDLINE | ID: mdl-36622106
Hepatitis C is a blood-borne virus that causes thousands of deaths from liver cirrhosis and liver cancer each year. Antiviral therapies can cure most cases of infection in 12 weeks. Unfortunately, treatment is expensive, and sticking with the regimen for 12 weeks can be difficult. It may be especially challenging for unhoused people or those who use injection drugs and who have high rates of hepatitis C infection. Shorter durations of therapy may make it more accessible, especially for high-risk populations. But studies of shorter antiviral treatment durations have yet to produce high enough cure rates. Finding ways to identify patients who would benefit from shorter therapy is a key goal of the World Health Organization. Potential characteristics that may predict a faster treatment response include low virus levels before initiating treatment, patient genetics, drug resistance mutations in the virus, and higher drug levels in the patient's blood during treatment. For example, previous research showed that a rapid decrease in virus levels in a patient's blood two days after starting antiviral therapy with three drugs predicted patient cures after three weeks of treatment. To test if high cure rates could be achieved in just four weeks of treatment, Flower et al. enrolled 52 patients with hepatitis C in a study to receive the most widely accessible dual antiviral treatment (sofosbuvir and daclatasvir). Participants received four or eight weeks of treatment, depending on the amount of viral RNA in their blood after two days of treatment. The results indicate that a rapid decrease in virus levels in the blood does not adequately predict cure rates with four weeks of two-drug combination therapy. However, eight weeks may be highly effective, regardless of viral levels early in treatment. Thirty-four individuals with low virus levels on the second day of treatment received four weeks of therapy, which cured 21 or 62% of them. All seventeen individuals with higher viral levels on day two were cured after eight weeks of treatment. Twelve weeks of retreatment was sufficient to cure the 13 individuals who did not achieve cure with four weeks of therapy. Even patients with drug resistance genes after the first round of therapy responded to a longer second round. Flower et al. show that patient genetics, virus subtype, drug levels in the patient's blood, and viral drug resistance genes before therapy, were not associated with patient cures after four weeks of treatment. Given that retreatment is safe and effective, larger studies are now needed to determine whether eight weeks of therapy with sofosbuvir and daclatasvir may be enough to cure patients with mild liver disease. More studies are also necessary to identify patients that may benefit from shorter therapy durations. Finding ways to shorten antiviral therapy for hepatitis C could help make treatment more accessible and reduce therapy costs for both individuals and governments.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis C / Hepatitis C Crónica Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Humans Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Vietnam Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis C / Hepatitis C Crónica Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Humans Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Vietnam Pais de publicación: Reino Unido