scholarly journals Hepatitis C Resistance-Associated Substitutions Among People Who Inject Drugs Treated with Direct-Acting Antiviral-Containing Regimens

2021 ◽  
Author(s):  
Matthew J Akiyama ◽  
Lindsey Riback ◽  
Jacqueline D Reeves ◽  
Yolanda S Lie ◽  
Linda Agyemang ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Protease Inhibitor ◽  
People Who Inject Drugs ◽  
Virologic Failure ◽  
Late Relapse ◽  
Resistant Virus ◽  
Genotype 1 ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Background Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) can contribute to virologic failure and limit retreatment options. People who inject drugs (PWID) are at highest risk for transmission of resistant virus. We report on RASs at baseline and following virologic failure in DAA-naive and protease inhibitor-experienced PWID. Methods We sequenced the NS3/4A, NS5A, and NS5B regions from 150 PWID with genotype 1 (GT1) viruses; 128 (85.3%) GT1a, 22 (14.7%) GT1b. Results Among the 139 (92.7%) DAA-naive PWID, 85/139 (61.2%) had baseline RASs – 67/139 (48.2%) in NS3 (predominantly Q80K/L); 25/139 (18.0%) in NS5A; and 8/139 (5.8%) in NS5B. Of the 11 protease inhibitor-experienced participants, 9 had baseline NS3 RASs (V36L N=1, Q80K N=9) and 4 had baseline NS5A RASs (M28V N=2, H58P N=1, A92T N=1). Among the 11 participants who had post-treatment samples with detectable virus (seven treatment failures, one late relapse, three reinfections), one sofosbuvir/ledipasvir failure had a baseline H58P. Two sofosbuvir/ledipasvir-treated participants developed new NS5A mutations (Q30H, Y93H, L31M/V). Otherwise, no RASs were detected. Conclusion Our results demonstrate RAS prevalence among DAA-naive PWID is comparable to that in the general population. Only 2/150 (1.3%) in our longitudinal cohort developed treatment-emergent RASs. Concern for transmission of resistant virus may therefore be minimal.

A survey of Australian general practitioners’ hepatitis C knowledge and management 2 years after subsidised direct-acting antiviral therapy became available

Sexual Health ◽  
2020 ◽  
Vol 17 (4) ◽  
pp. 387
Author(s):  
Michelle Gooey ◽  
Evelyn Wong ◽  
Alisa Pedrana ◽  
Nicole Allard ◽  
Joseph Doyle ◽  
...  
Keyword(s):  
Primary Care ◽  
Hepatitis C ◽  
General Practitioners ◽  
People Who Inject Drugs ◽  
Knowledge Score ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Additional Support ◽  
Direct Acting

In 2016, hepatitis C direct-acting antivirals (DAAs) became available in Australia. A group of general practitioners (GPs) were surveyed twice to assess hepatitis C knowledge and management; 191/1000 (19.1%) responded at baseline, 164/938 (17.5%) at follow up. Participants’ mean Knowledge score increased: baseline 5.75 (95% CI 5.61–5.91), follow up 6.09 (95% CI 5.95–6.22; P <0.01). At follow up, 36/163 (22%) had prescribed DAAs compared with 23/187 (12%) at baseline (χ2(1) = 5.95, P = 0.02); however, 67/150 (45%) were unsure of treatment eligibility for people who inject drugs. Additional support for GPs is warranted to ensure optimal hepatitis C management in primary care.

scholarly journals Computer-aided identification of a series of novel ligands showing high potency as hepatitis C virus NS3/4A protease inhibitors

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Stephen Ejeh ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Stephen E. Abechi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Binding Energy ◽  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Antiviral Agents ◽  
High Potency ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Abstract Background Hepatitis C virus (HCV) is a global medical condition that causes several life-threatening chronic diseases in the liver. The conventional interferon-free treatment regimens are currently in use by a blend of direct-acting antiviral agents (DAAs) aiming at the viral NS3 protease. However, major concerns may be the issue of DAA-resistant HCV strains and the limited availability to the DAAs due to their high price. Due to this crisis, the developments of a new molecule with high potency as an NS3/4A protease inhibitor of the hepatitis-C virus remain a high priority for medical research. This study aimed to use in-silico methods to identify high potent molecule as an NS3/4A protease inhibitor and investigating the binding energy of the identified molecule in comparison with approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) through molecular docking. Results The model obtained by in-silico method have the following statistical records, coefficient of determination (r2) of 0.7704, cross-validation (q2LOO = 0.6914); external test set (r2(pred) = 0.7049) and Y-randomization assessment (cR2p = 0.7025). The results from the model were used to identify 12 new potential human HCV NS3/4A protease inhibitors, and it was observed that the identified molecule is well-fixed when docked with the receptor and was found to have the lowest binding energy of − 10.7, compared to approved direct-acting antiviral agents (Telaprevir, Simeprevir, and Voxilaprevir) with − 9.5, − 10.0, − 10.5 binding energy, respectively. Conclusion The binding affinity (− 10.7) of the newly identified molecule docked with 3D structures of HCV NS3/4a protease/helicase (PDB ID: 4A92) was found to be better than that of Telaprevir, Simeprevir, and Voxilaprevir (approved direct-acting antiviral agents) which are − 9.5, − 10.0, and − 10.5, respectively. Hence, a novel molecule was identified showing high potency as HCV NS3/4a protease inhibitors.

scholarly journals Hepatitis C Virus Treatment Access Among Human Immunodeficiency Virus and Hepatitis C Virus (HCV)-Coinfected People Who Inject Drugs in Guangzhou, China: Implications for HCV Treatment Expansion

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Carissa E. Chu ◽  
Feng Wu ◽  
Xi He ◽  
Kali Zhou ◽  
Yu Cheng ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Social Workers ◽  
People Who Inject Drugs ◽  
Hiv Treatment ◽  
Direct Acting Antivirals ◽  
Hcv Treatment ◽  
Treatment Access ◽  
Immunodeficiency Virus ◽  
Direct Acting

Abstract Background.  Hepatitis C virus (HCV) treatment access among human immunodeficiency virus (HIV)/HCV-coinfected people who inject drugs is poor, despite a high burden of disease in this population. Understanding barriers and facilitators to HCV treatment uptake is critical to the implementation of new direct-acting antivirals. Methods.  We conducted in-depth interviews with patients, physicians, and social workers at an HIV treatment facility and methadone maintenance treatment centers in Guangzhou, China to identify barriers and facilitators to HCV treatment. We included patients who were in various stages of HCV treatment and those who were not treated. We used standard qualitative methods and organized data into themes. Results.  Interview data from 29 patients, 8 physicians, and 3 social workers were analyzed. Facilitators and barriers were organized according to a modified Consolidated Framework for Implementation Research schematic. Facilitators included patient trust in physicians, hope for a cure, peer networks, and social support. Barriers included ongoing drug use, low HCV disease knowledge, fragmented reimbursement systems, HIV exceptionalism, and stigma. Conclusions.  Expanding existing harm reduction programs, HIV treatment programs, and social services may facilitate scale-up of direct-acting antivirals globally. Improving integration of ancillary social and mental health services within existing HIV care systems may facilitate HCV treatment access.

Hepatitis C “true” late relapse beyond 48 weeks of sustained virologic response after direct acting antiviral therapy

2017 ◽  
Vol 66 (4) ◽  
pp. 862-863 ◽  
Author(s):  
Thomas Klag ◽  
Julia Dietz ◽  
Christoph R. Werner ◽  
Julia M. Schwarz ◽  
Ulrich M. Lauer ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Therapy ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Late Relapse ◽  
Direct Acting Antiviral ◽  
Direct Acting
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