Direct-Acting Antiviral Agents and the Path to Interferon Independence

Schmidt, Warren N.; Nelson, David R.; Pawlotsky, Jean‐Michel; Sherman, Kenneth E.; Thomas, David L.; Chung, Raymond T.

doi:10.1016/j.cgh.2013.06.024

Cited by 37 publications

(34 citation statements)

References 47 publications

(57 reference statements)

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“…Daclatasvir (DCV) and ledipasvir (LDV) are examples of NS5A inhibitors [171] . With the advent and improvement of DAAs, drugs now can target almost all steps of the HCV life cycle, including entry, translation, RNA replication, assembly, and export of progeny viruses [175] . This has facilitated the designing of highly potent oral drugs characterized by shorter treatment duration, simplified dosing, a high genetic barrier to resistance, and improved safety profiles [176] .…”

Section: Hcv Ns5a Inhibitorsmentioning

confidence: 99%

Hepatitis C genotype 4: The past, present, and future

Abdel-Ghaffar

Sira

Naghi

2015

WJH

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Hepatitis C virus (HCV) genotype (GT) 4 represents 12%-15% (15-18 million) of total global HCV infection. It is prevalent in Northern and Equatorial Africa and the Middle East, and is also present in some countries in Europe. GT-4 (and subtype 4a in particular) dominates the HCV epidemic in Egypt. In underdeveloped countries, risk factors associated with HCV infection may be due to unsafe medical practices or other factors such as familial transmission, mother's HCV status, or illiteracy. HCV prevention and control programs should include health education, increased community awareness towards the disease, controlling infection distribution in healthcare centers, proper sterilization of medical and dental instruments, and ensuring safe supply of blood and blood-products. Response rates to a 48-wk combined pegylated-interferon (PEG-IFN) and ribavirin (RBV) treatment range from 40%-69%, and HCV-GT-4 has been considered better than GT-1 but worse than GT-2 and GT-3 in treatment with PEG-IFN/RBV. However, with the introduction of the HCV-GT-1 effective protease inhibitors boceprevir and telaprevir in 2011, HCV-GT-4 became the "most difficult (GT) to treat". Recently, the direct-acting antivirals (DAAs) with pan-genotypic activities simeprevir, sofosbuvir, and daclatasvir have been recommended in triple regimens with PEG-IFN/RBV for the treatment of HCV-GT-4. An IFN-free regimen will be available for treatment of all genotypes of HCV in the near future. To date, several DAAs have been developed and are currently being evaluated in various combinations in clinical trials. As new regimens and new agents are being approved by the Food and Drug Administration, we can expect the guidelines for HCV treatment to be changed. The availability of shorter, simpler, and more tolerable treatment regimens can reduce the morbidity and mortality associated with HCV infection. With such a large number of therapeutic agents available, we can end up with a range of choices that we can select from to treat patients.

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Section: Hcv Ns5a Inhibitorsmentioning

confidence: 99%

Hepatitis C genotype 4: The past, present, and future

Abdel-Ghaffar

Sira

Naghi

2015

WJH

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“…Advances in HCV treatments can now cure more than 90 % of chronically infected individuals using interferonfree, short-term, well-tolerated regimens. [10][11][12][13][14] New treatment regimens present important public health opportunities to reduce HCV-related morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

Results from a Geographically Focused, Community-Based HCV Screening, Linkage-to-Care and Patient Navigation Program

et al. 2015

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BACKGROUND: Many of the five million Americans chronically infected with hepatitis C (HCV) are unaware of their infection and are not in care. OBJECTIVE: We implemented and evaluated HCV screening and linkage-to-care interventions in a community setting. DESIGN: We developed a comprehensive, communitybased HCV screening and linkage-to-care program in a medically underserved neighborhood with high rates of HCV infection in Philadelphia, Pennsylvania. We provided patient navigation services to enroll uninsured patients in insurance programs, facilitate referrals from primary care physicians and link patients to an HCV infectious disease specialist with intention to treat and cure. PATIENTS: Philadelphia residents were recruited through street outreach. MAIN MEASURES: We measured anti-HCV seroprevalence and diagnosis, linkage and retention in care outcomes for chronically infected patients. KEY RESULTS: We screened 1,301 participants for HCV; anti-HCV seroprevalence was 3.9 % and 2.8 % of all patients were chronically infected. Half of chronically infected patients were newly diagnosed; the remaining patients were aware of infection but not in care. We provided confirmatory RNA testing and results, assisted patients with attaining insurance and linked most chronically infected patients to a primary care provider. The biggest barrier to retaining patients in care was obtaining referrals for subspecialty providers; however, we obtained referrals for 64 % of chronically infected participants and have retained most in subspecialty HCV care. Several have commenced treatment. CONCLUSIONS: Non-clinical screening programs with patient navigator services are an effective means to diagnose, link, retain and re-engage patients in HCV care. Eliminating referral requirements for subspecialty care might further enhance retention in care for patients chronically infected with HCV.KEY WORDS: hepatitis C; HCV screening; community-based screening; patient navigation; continuum of care. J Gen Intern Med 30(7):950-7

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“…[1][2][3] The only interferon-free option currently approved by the Food and Drug Administration for the treatment of HCV genotype 1 infection is 24 weeks of sofosbuvir and ribavirin for patients who are ineligible to receive interferon; the reported response rate is 68%. 4 Interferon treatment is associated with a number of side effects, including influenza-like symptoms, depression, and cytopenia.…”

mentioning

confidence: 99%