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1.
Viruses ; 13(7)2021 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-34372520

RESUMEN

The 2019 novel coronavirus (COVID-19) pandemic has placed a significant strain on hepatitis programs and interventions (screening, diagnosis, and treatment) at a critical moment in the context of hepatitis C virus (HCV) elimination. We sought to quantify changes in Direct Acting Antiviral (DAA) utilization among different countries during the pandemic. We conducted a cross-sectional time series analysis between 1 September 2018 and 31 August 2020, using the IQVIA MIDAS database, which contains DAA purchase data for 54 countries. We examined the percent change in DAA units dispensed (e.g., pills and capsules) from March to August 2019 to the same period of time in 2020 across the 54 countries. Interrupted time-series analysis was used to examine the impact of COVID-19 on monthly rates of DAA utilization across each of the major developed economies (G7 nations). Overall, 46 of 54 (85%) jurisdictions experienced a decline in DAA utilization during the pandemic, with an average of -43% (range: -1% in Finland to -93% in Brazil). All high HCV prevalence (HCV prevalence > 2%) countries in the database experienced a decline in utilization, average -49% (range: -17% in Kazakhstan to -90% in Egypt). Across the G7 nations, we also observed a decreased trend in DAA utilization during the early months of the pandemic, with significant declines (p < 0.01) for Canada, Germany, the United Kingdom, and the United States of America. The global response to COVID-19 led to a large decrease in DAA utilization globally. Deliberate efforts to counteract the impact of COVID-19 on treatment delivery are needed to support the goal of HCV elimination.


Asunto(s)
Antivirales/administración & dosificación , COVID-19/tratamiento farmacológico , Antivirales/normas , Brasil/epidemiología , COVID-19/epidemiología , Canadá/epidemiología , Estudios Transversales , Egipto/epidemiología , Finlandia/epidemiología , Alemania/epidemiología , Hepacivirus/aislamiento & purificación , Hepatitis C , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Kazajstán/epidemiología , Pandemias , Prevalencia , SARS-CoV-2/aislamiento & purificación , Reino Unido/epidemiología , Estados Unidos
2.
Pharmaceut Med ; 35(4): 203-213, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34453703

RESUMEN

The Emergency Use Authorization (EUA) originated in 2004 because of the need for emergency medical countermeasures (MCMs) against potential bioterrorist attacks. The EUA also proved useful in dealing with subsequent pandemics and has emerged as a critical regulatory pathway for therapeutics and vaccines throughout the Coronavirus Disease 2019 (COVID-19) pandemic. With the EUA process in the USA, we witnessed emergency authorizations, their expansions, as well as withdrawal of previously authorized products, which exemplifies the dynamic nature of scientific review of EUA products. EUAs proved vital for the first group of COVID-19 vaccines, including the temporary pause of one vaccine while emergency safety issues were evaluated. Although this review on the EUA is primarily focused on the USA, distinctions were made with other jurisdictions such as Europe and Canada with respect to the emergency authorizations of the vaccines. Finally, we discuss some important differences following EUA and formal new drug/vaccine application (NDA/BLA) approvals.


Asunto(s)
Antivirales/normas , Vacunas contra la COVID-19/normas , COVID-19/prevención & control , Aprobación de Drogas/legislación & jurisprudencia , Urgencias Médicas/historia , Antivirales/administración & dosificación , Antivirales/efectos adversos , Bioterrorismo/historia , Bioterrorismo/prevención & control , COVID-19/tratamiento farmacológico , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Canadá/epidemiología , Defensa Civil/historia , Aprobación de Drogas/historia , Urgencias Médicas/epidemiología , Europa (Continente)/epidemiología , Historia del Siglo XXI , Humanos , Pandemias/prevención & control , Estados Unidos/epidemiología
3.
Anal Bioanal Chem ; 413(23): 5811-5820, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34302183

RESUMEN

Remdesivir is a nucleotide analog prodrug that has received much attention since the outbreak of the COVID-19 pandemic in December 2019. GS-441524 (Nuc) is the active metabolite of remdesivir and plays a pivotal role in the clinical treatment of COVID-19. Here, a robust HPLC-MS/MS method was developed to determine Nuc concentrations in rat plasma samples after a one-step protein precipitation process. Chromatographic separation was accomplished on Waters XBrige C18 column (50 × 2.1 mm, 3.5 µm) under gradient elution conditions. Multiple reaction monitoring transitions in electrospray positive ion mode were m/z 292.2 → 163.2 for Nuc and 237.1 → 194.1 for the internal standard (carbamazepine). The quantitative analysis method was fully validated in line with the United States Food and Drug Administration guidelines. The linearity, accuracy and precision, matrix effect, recovery, and stability results met the requirements of the guidelines. Uncertainty of measurement and incurred sample reanalysis were analyzed to further ensure the robustness and reproducibility of the method. This optimized method was successfully applied in a rat pharmacokinetics study of remdesivir (intravenously administration, 5 mg kg-1). The method can act as a basis for further pharmacokinetic and clinical efficacy investigations in patients with COVID-19. Graphical abstract.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirales/sangre , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Adenosina/sangre , Adenosina/farmacocinética , Adenosina/normas , Adenosina Monofosfato/sangre , Adenosina Monofosfato/farmacocinética , Adenosina Monofosfato/normas , Alanina/sangre , Alanina/farmacocinética , Alanina/normas , Animales , Antivirales/farmacocinética , Antivirales/normas , Límite de Detección , Masculino , Control de Calidad , Ratas , Ratas Sprague-Dawley , Estándares de Referencia , Reproducibilidad de los Resultados
4.
Viruses ; 13(3)2021 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-33800289

RESUMEN

The availability of all oral direct acting antiviral agents (DAAs) has revolutionized the management of HCV infections in recent years, allowing to achieve a sustained virological response (SVR) in more than 95% of cases, irrespective of hepatitis C Virus (HCV) genotype or staging of liver disease. Although rare, the failure to the latest-generation regimens (grazoprevir/elbasvir, sofosbuvir/velpatasvir, pibrentasvir/glecaprevir) represents a serious clinical problem, since the data available in the literature on the virological characteristics and management of these patients are few. The aim of the present narrative review was to provide an overview of the impact of baseline RASs in patients treated with the latest-generation DAAs and to analyze the efficacy of the available retreatment strategies in those who have failed these regimens.


Asunto(s)
Antivirales/normas , Farmacorresistencia Viral/genética , Hepatitis C/tratamiento farmacológico , Insuficiencia del Tratamiento , Antivirales/farmacología , Antivirales/uso terapéutico , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Hepacivirus/efectos de los fármacos , Hepatitis C/virología , Humanos , Retratamiento , Respuesta Virológica Sostenida
5.
Viruses ; 13(4)2021 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-33804814

RESUMEN

The disinfection of surfaces in medical facilities is an important element of infection control, including the control of viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preparations used for surface disinfection are typically characterized via their activity against test organisms (i.e., viruses, bacteria and fungi) in the laboratory. Typically, these methods use a suspension of the test organism to assess the bactericidal, fungicidal or virucidal activity of a given preparation. However, such suspension methods do not fully imitate real-life conditions. To address this issue, carrier methods have been developed, in which microorganisms are applied to the surface of a carrier (e.g., stainless steel, glass and polyvinyl chloride (PVC)) and then dried. Such methods more accurately reflect the applications in real-life clinical practice. This article summarizes the available methods for assessing the virucidal activity of chemical disinfectants for use in medical facilities based on the current European standards, including the activity against coronaviruses.


Asunto(s)
Antivirales/farmacología , Desinfectantes/farmacología , SARS-CoV-2/efectos de los fármacos , Antivirales/normas , COVID-19/prevención & control , COVID-19/virología , Desinfectantes/normas , Europa (Continente) , Humanos , SARS-CoV-2/crecimiento & desarrollo
6.
J Hosp Infect ; 111: 180-183, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33582201

RESUMEN

The outbreak of the SARS-CoV-2 pandemic is triggering a global health emergency alert. Until vaccination becomes available, a bundle of effective preventive measures is desperately needed. Recent research is indicating the relevance of aerosols in the spread of SARS-CoV-2. Thus, in this study commercially available antiseptic mouthwashes based on the active ingredients chlorhexidine digluconate and octenidine dihydrochloride (OCT) were investigated regarding their efficacy against SARS-CoV-2 using the European Standard 14476. Based on the requirement of EN 14476 in which reduction of at least four decimal logarithms (≥4 log10) of viral titre is requested to state efficacy, the OCT-based formulation was found to be effective within a contact time of only 15 s against SARS-CoV-2. Based on this in-vitro data the OCT mouthwash thus constitutes an interesting candidate for future clinical studies to prove its effectiveness in a potential prevention of SARS-CoV-2 transmission by aerosols.


Asunto(s)
Antiinfecciosos Locales/normas , Antivirales/farmacología , Antivirales/normas , COVID-19/prevención & control , Clorhexidina/farmacología , Clorhexidina/normas , Antisépticos Bucales/normas , Antiinfecciosos Locales/farmacología , Humanos , Pandemias , Estándares de Referencia , SARS-CoV-2
7.
J Hosp Infect ; 110: 103-107, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33484783

RESUMEN

It can be a diagnostic challenge to identify patients with coronavirus disease 2019 in whom antibiotics can be safely withheld. This study evaluated the effectiveness of a guideline implemented at Sheffield Teaching Hospitals NHS Foundation Trust that recommends withholding antibiotics in patients with low serum procalcitonin (PCT), defined as ≤0.25 ng/mL. Results showed reduced antibiotic consumption in patients with PCT ≤0.25 ng/mL with no increase in mortality, alongside a reduction in subsequent carbapenem prescriptions during admission. The results support the effectiveness of this guideline, and further research is recommended to identify the optimal cut-off value for PCT in this setting.


Asunto(s)
Antibacterianos/normas , Antibacterianos/uso terapéutico , Antivirales/normas , Antivirales/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , COVID-19/tratamiento farmacológico , Polipéptido alfa Relacionado con Calcitonina/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Programas de Optimización del Uso de los Antimicrobianos/métodos , Infecciones Bacterianas/sangre , Biomarcadores/sangre , Estudios de Cohortes , Coinfección/sangre , Coinfección/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Adulto Joven
9.
Virulence ; 12(1): 188-194, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33356842

RESUMEN

HBV pol plays a critical role in the replication of hepatitis B virus (HBV). Previous studies conducted on HBV pol have produced limited evidence on HBV pol expression due to the lack of effective detection methods. The present study used the HBV pol (159-406 aa) protein as a target to screen for specific monoclonal antibodies that recognize HBV pol and subsequently evaluate their diagnostic and therapeutic value. Four antibodies (P3, P5, P12, P20) against HBV pol were obtained. Among them, the P20 antibody indicated optimal binding with HBV pol as demonstrated by Western blotting (WB) in a cell model transfected with the HBV genome. We also expressed P5 and P12 antibodies in mouse liver cells by transfection and the results indicated significant antiviral effects caused by these two antibodies especially P12. In summary, the present study established an antibody which was denoted P20. This antibody can be used to detect HBV pol expression by four HBV genomes via WB analysis. In addition, the antibody denoted P12 could exert antiviral effects via intracellular expression, which may provide a promising approach for the treatment of chronic hepatitis B.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Antivirales/inmunología , Antivirales/normas , ADN Polimerasa Dirigida por ADN/inmunología , Virus de la Hepatitis B/inmunología , Animales , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/aislamiento & purificación , Línea Celular Tumoral , ADN Polimerasa Dirigida por ADN/genética , Células Hep G2 , Virus de la Hepatitis B/enzimología , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/terapia , Humanos , Ratones , Inhibidores de la Síntesis del Ácido Nucleico
11.
Crit Care ; 24(1): 584, 2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32993740

RESUMEN

BACKGROUND: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients. The aim of this study was to assess current evidence to determine whether antiviral therapy is associated with better outcomes in these patients. METHODS: MEDLINE, ISI Web of Science, Cochrane Database and ClinicalTrials.gov were searched from inception to 25 May 2020. All clinical studies investigating the effects of antiviral therapy on the outcome of mechanically ventilated ICU patients in whom HSV was detected in the respiratory tract were eligible for inclusion, regardless of study design, publication status or language. Titles and abstracts were reviewed independently by two authors. If the articles seemed eligible, full-text articles were reviewed and data extracted. We performed a random-effects meta-analysis to estimate relative risks (RRs) with corresponding 95% confidence intervals (CIs). The primary endpoint was hospital all-cause mortality. RESULTS: Nine studies were included in the meta-analysis (one randomized controlled trial, eight cohort studies). Antiviral treatment was associated with lower hospital mortality (with antiviral treatment, 40.6% (189 out of 465 patients); without, 52.7% (193 out of 366 patients); RR 0.74 [0.64, 0.85]; eight studies, low quality of evidence). Furthermore, antiviral treatment was associated with lower 30-day mortality (RR 0.75 [0.59, 0.94]; three studies, very low quality of evidence). We did not observe evidence for differences in ICU mortality (RR 0.73 [0.51, 1.05]; three studies, very low quality of evidence). CONCLUSIONS: This meta-analysis of the available data shows that antiviral therapy might result in lower hospital and 30-day all-cause mortality in mechanically ventilated ICU patients who are positive for HSV in the respiratory tract. However, this result must be interpreted with great caution due to the high risk of bias and limited number of patients. Large, well-designed randomized controlled clinical trials are urgently needed. TRIAL REGISTRATION: The study was registered in advance on International Prospective Register of Systematic Reviews (CRD42020180053) .


Asunto(s)
Antivirales/normas , Sistema Respiratorio/virología , Simplexvirus/efectos de los fármacos , Antivirales/farmacología , Antivirales/uso terapéutico , Mortalidad Hospitalaria/tendencias , Humanos , Tiempo de Internación/tendencias , Respiración Artificial/métodos , Sistema Respiratorio/efectos de los fármacos , Simplexvirus/patogenicidad , Simplexvirus/fisiología
13.
JAMA Netw Open ; 3(7): e2011055, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32692371

RESUMEN

Importance: Direct-acting antiviral (DAA) drugs are highly effective in curing hepatitis C virus (HCV) infection. Previous simulations showed extended life as a key health advantage of DAA drugs, but real-world evidence on the association between DAA treatment and reduced mortality is limited. Objectives: To examine the association of DAA treatment with mortality among Medicare beneficiaries with hepatitis C. Design, Setting, and Participants: This cohort study used Medicare claims data of beneficiaries who sought hepatitis C care for the first time between January 1, 2014, and December 31, 2016, after at least a 1-year washout period. Medicare Part D files were used in identifying DAA therapy initiation and completion. Death dates, demographic data, and indicators of health risks were obtained from the Master Beneficiary Summary Files. Beneficiaries with hepatitis C were considered as patients with DAA treatment if they initiated DAA therapy during the study period. Beneficiaries with hepatitis C who did not initiate DAA therapy during the study period were considered as patients without DAA treatment. Patients without DAA treatment were selected using 1-to-1 propensity score matching. Data were analyzed between September 1, 2019, and March 31, 2020. Exposures: Completion of DAA treatment. Main Outcomes and Measures: Time to death from the index date of seeking hepatitis C care after at least a 1-year washout period. Cox proportional hazards regression models with time-varying exposure were used to compare mortality rates between propensity score-matched cohorts of patients with DAA treatment and those without DAA treatment. Separate analyses were performed for patients with or without cirrhosis. Heterogeneity in the association between DAA treatment and mortality by sex and dual-eligibility status was examined. Results: A propensity score-matched sample of 51 478 Medicare beneficiaries with a mean (SD) age of 59.4 (11.1) years and 30 473 men (59.2%) was assessed. Of this total, 8240 patients (16.0%) had cirrhosis (5224 men [63.4%]; mean [SD] age, 62.3 [9.7] years) and 43 238 patients (84.0%) had no cirrhosis (25 249 men [58.4%]; mean [SD] age, 58.8 [11.3] years). The adjusted hazard ratio (HR) of dying between patients with DAA treatment and those without DAA treatment in the cirrhosis group was 0.51 (95% CI, 0.46-0.57). The association of DAA treatment with mortality did not differ by sex (women vs men: HR, 0.46 [95% CI, 0.38-0.56] vs HR, 0.53 [95% CI, 0.47-0.60]; P = .27) or dual-eligibility status (non-dual-eligible HR, 0.52 [95% CI, 0.43-0.63] vs dual-eligible HR, 0.50 [95% CI, 0.44-0.57]; P = .80) in the cirrhosis group. The adjusted HR of dying between patients with DAA treatment and those without DAA treatment among patients without cirrhosis was 0.54 (95% CI, 0.50-0.58). The association of DAA treatment with mortality did not differ by sex (women vs men: HR, 0.53 [95% CI, 0.46-0.60] vs HR, 0.55 [95% CI, 0.50-0.60]; P = .66) among patients without cirrhosis. However, the survival advantage associated with DAAs for non-dual-eligible beneficiaries was statistically significantly higher than for dual-eligible beneficiaries among patients without cirrhosis (HR, 0.47 [95% CI, 0.41-0.55] vs HR, 0.57 [95% CI, 0.52-0.62]; P = .02). Conclusions and Relevance: In this cohort study, DAA treatment appeared to be associated with a decrease in mortality among Medicare beneficiaries with or without cirrhosis. These findings suggest that increasing access to DAA drugs for all patients with HCV infection, regardless of disease progression, could improve population health.


Asunto(s)
Antivirales/normas , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/mortalidad , Medicare/estadística & datos numéricos , Anciano , Antivirales/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estados Unidos
14.
Medicine (Baltimore) ; 99(17): e19765, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32332615

RESUMEN

BACKGROUND: Congenital cytomegalovirus (CMV) disease, a common mother-to-child infection, can lead to neurological sequelae. Some clinical trials have shown that oral valganciclovir (VGCV) can improve hearing and neurodevelopmental impairment in infants with congenital CMV disease. However, VGCV has neither been approved in Japan nor other countries as a treatment for this disease by the government health insurance. METHODS: This study is a non-randomized, prospective, open-label, multicenter, single-arm clinical trial and will include subjects meeting the following criteria: confirmation of positive CMV-DNA amplification in urine by an in vitro diagnostic test within 21 days of age; congenital CMV disease with one or more central nervous system disorders-microcephaly, hydrocephalus or ventricular enlargement, periventricular calcification, cortical hypoplasia or white matter injury, retinal choroiditis, and abnormal auditory brainstem response (ABR); and infants within 2 months of age with a gestational age ≥32 weeks at birth and weighing ≥1800 g at the time of registration. Subjects will be orally administered 16 mg/kg VGCV twice daily for 6 months. The target number of cases for enrollment between February 3, 2020 and July 31, 2021 is 25. Primary endpoint is the change in whole blood CMV loads before and after 6 months of treatment. The important secondary endpoint is the change in ABR (both best and total ear hearing assessments) before and after 6 months of treatment. The safety endpoints are adverse events and drug side effects. DISCUSSION: To the best of our knowledge, this multicenter, open-label, single-arm study will be the first well-designed clinical trial to evaluate the efficacy of oral VGCV in infants with congenital CMV diseases. The findings will reveal the efficacy and safety of oral VGCV treatments and enable the approval of oral VGCV as a treatment for infants with congenital CMV disease by the government health insurance of Japan.


Asunto(s)
Protocolos Clínicos , Infecciones por Citomegalovirus/tratamiento farmacológico , Valganciclovir/normas , Administración Oral , Antivirales/normas , Antivirales/uso terapéutico , Citomegalovirus/efectos de los fármacos , Citomegalovirus/patogenicidad , Femenino , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Japón , Masculino , Estudios Prospectivos , Valganciclovir/uso terapéutico
15.
Antiviral Res ; 177: 104762, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32147496

RESUMEN

Recent publications have brought attention to the possible benefit of chloroquine, a broadly used antimalarial drug, in the treatment of patients infected by the novel emerged coronavirus (SARS-CoV-2). The scientific community should consider this information in light of previous experiments with chloroquine in the field of antiviral research.


Asunto(s)
Antivirales/uso terapéutico , Cloroquina/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Antivirales/efectos adversos , Antivirales/farmacología , Antivirales/normas , Betacoronavirus/efectos de los fármacos , COVID-19 , China , Cloroquina/efectos adversos , Cloroquina/farmacología , Cloroquina/normas , Ensayos Clínicos como Asunto/normas , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/farmacología , Hidroxicloroquina/normas , Hidroxicloroquina/uso terapéutico , Pandemias , SARS-CoV-2
16.
Lancet Gastroenterol Hepatol ; 5(4): 374-392, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31954439

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) prevalence estimates for adults and high-risk groups have been widely published, but the disease burden in children is poorly understood. Direct-acting antiviral drugs, which are considered to be highly effective curative therapies for HCV, are now approved for paediatric patients as young as 3 years. Reliable prevalence estimates for this population are needed to inform scale-up of treatment and national strategies. This analysis combines past modelling and epidemiological work in 104 countries and territories to estimate global HCV prevalence in children in 2018. METHODS: In this modelling study, a comprehensive literature review for articles published between Jan 1, 2000, and March 31, 2019, was used to determine historical HCV prevalence estimates in children in all 249 countries and territories of the world. We identified published HCV prevalence estimates for children aged 0-18 years who are not at high risk of HCV infection in 39 countries and territories and inputted them into dynamic Markov disease-burden models to estimate viraemic HCV prevalence in 2018. For 25 of them, which had complete data, available information on HCV prevalence in children was used to build regression models to predict paediatric prevalence in an additional 65 countries and territories that had country-specific or territory-specific data about predictors only. Regression models were created for each 5-year paediatric age cohort from 0 to 19 years, considering several predictor variables. The data and forecasts from the 104 countries and territories for which data were available were used to calculate HCV prevalence by Global Burden of Disease region, which was then applied to the remaining 145 countries and territories to generate a global estimate. FINDINGS: The global estimate for viraemic prevalence in the paediatric population aged 0-18 years was 0·13% (95% uncertainty interval 0·08-0·16), corresponding to 3·26 million (2·07-3·90) children with HCV in 2018. HCV prevalence increased with age in all countries and territories. HCV prevalence in women of childbearing age was the strongest predictor of HCV prevalence in children aged 0-4 years (p<0·0001). Prevalence of HCV in adults was significantly associated with HCV prevalence in children aged 5-19 years (p<0·0001), and the proportion of HCV infections in people who inject drugs was significantly associated with HCV prevalence in children aged 15-19 years (p=0·036). INTERPRETATION: Most studies on HCV prevalence in children focus on high-risk groups and highly endemic geographic areas. Our analysis provides global prevalence estimates of HCV in the paediatric population. Treatment in paediatric patients requires different clinical and population health management optimisation than in adults. Because of this heterogeneity, country-specific or territory-specific and age-specific HCV prevalence estimates can help countries and territories to improve national HCV elimination strategies. FUNDING: Gilead Sciences, John C Martin Foundation, and private donors.


Asunto(s)
Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Viremia/epidemiología , Adolescente , Antivirales/normas , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Carga Global de Enfermedades/tendencias , Hepacivirus/aislamiento & purificación , Humanos , Lactante , Recién Nacido , Masculino , Modelos Teóricos , Prevalencia , Factores de Riesgo , Adulto Joven
17.
J Viral Hepat ; 27(3): 243-260, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31664755

RESUMEN

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Perdida de Seguimiento , Factores de Edad , Antivirales/normas , Bencimidazoles/uso terapéutico , Colombia Británica , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Fluorenos/uso terapéutico , Genotipo , Hepacivirus/genética , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , Resultado del Tratamiento
18.
New Microbiol ; 42(4): 189-196, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31609453

RESUMEN

Safety, efficacy, and predictor factors of sustained-virological-response after 24 weeks of new direct-acting antivirals were evaluated in hepatitis C virus patients with different stages of hepatic disease. 260 patients, median age 60 years, of whom 48.1% cirrhotics, 17.7% liver transplant recipients, and 45.7% naïve were treated with Sofosbuvir+Ribavirine, Sofosbuvir+Simeprevir±Ribavirine, Sofosbuvir+Daclatasvir± Ribavirine, Sofosbuvir+Ledispavir±Ribavirine, Ombitasvir/Paritaprevir/Ritonavir+Ribavirine and Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirine. Therapy outcomes, hematochemical parameters, viral replication, genotype, and resistance-associated-mutations were analyzed retrospectively. Sustained virological response was 90.4% in the whole population, 83.2% in cirrhotics, 85% in patients with previous virological failure, 93.6% in patients >60 years, and 95.6% in liver transplant recipients. SVR24 for each drug regimen was 75% Sofosbuvir+Ribavirine, 80.4% Sofosbuvir+Simeprevir±Ribavirine, 94.3% Sofosbuvir+Daclatasvir±Ribavirine, 98.7% Sofosbuvir+Ledispavir±Ribavirine, 100% Ombitasvir/ Paritaprevir/Ritonavir+Ribavirine and Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirine. The highest sustained virological response rates were obtained with genotype-1b (95.9%). Twenty-five patients, mostly cirrhotics or suffering from severe liver complications, manifested relapse (84%), breakthrough (12%), or non-response (4%). Mild side effects were observed in 41.1% of patients. Model-for-End-Liver- Disease score <10 and alanine aminotransferase ≤20 U/L at week 8 of therapy proved positive predictors of sustained virological response. Direct-acting antiviral therapy is efficacious and safe even in patients with advanced liver disease and/ or previous virological failure; Model-for-End-Liver-Disease <10 and alanine aminotransferase reduction during therapy were found to be reliable predicting markers of sustained-virological-response.


Asunto(s)
Antivirales , Hepatitis C , Antivirales/administración & dosificación , Antivirales/normas , Biomarcadores Farmacológicos/análisis , Quimioterapia Combinada , Genotipo , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Compuestos Macrocíclicos/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Ribavirina/administración & dosificación , Ritonavir/administración & dosificación , Simeprevir/administración & dosificación , Sofosbuvir/administración & dosificación , Sulfonamidas/administración & dosificación , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/análogos & derivados
19.
J Med Virol ; 91(6): 1104-1111, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30695109

RESUMEN

BACKGROUND: A real-life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. METHODS: We analyzed 590 consecutively enrolled patients with CHC-1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance-associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. RESULTS: The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24-week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV-"indeterminate" patients was not difference 95.0% in the RAV-negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. CONCLUSIONS: Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC-1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.


Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Respuesta Virológica Sostenida , Anciano , Antivirales/normas , Carcinoma Hepatocelular/virología , Estudios de Cohortes , Farmacorresistencia Viral , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Humanos , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
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