Effectiveness and tolerability of direct-acting antivirals for chronic hepatitis C patients in a Southern state of Brazil

ABSTRACT Background This study aimed to evaluate the clinical effectiveness in terms of sustained virological response and tolerability of available second generation direct-acting antivirals in Brazilian patients. Methods This was a retrospective observational study conducted in six centers in Southern Brazil. The sample comprised adult patients who were chronically infected with hepatitis C virus, regardless of virus genotype, fibrosis stage, or prior treatment. Statistical analysis was performed to compare the effectiveness among the treatments, and also to uncover the factors influencing the achievement of sustained virological response. Results A total of 296 patients were included in the study, with the majority receiving sofosbuvir with daclatasvir (59%) or sofosbuvir with simeprevir (26%). Overall sustained virological response rates were approximately 91.6%. For genotype 1, sofosbuvir with daclatasvir had an sustained virological response rate of approximately 95%, while the sustained virological response rate of sofosbuvir with simeprevir was 92%; this difference was statistically significant only for subtype 1b. The only treatment used for genotype 3 patients was sofosbuvir with daclatasvir, and lower rates of sustained virological response were observed for this group, compared to genotype 1 (84% versus 95%, p < 0.05). Apart from this difference between genotypes, and a difference between patients who achieved rapid virologic response compared with those who did not, there were no other statistically significant factors associated with sustained virological response. Conclusions The results point to the effectiveness of second-generation direct-acting antivirals in hepatitis C virus Brazilian patients, especially those with genotype 1. Furthermore, that patients with genotype 3 need more attention and adjustments in available treatment options.

Efficacy and cost effectiveness of combined conventional interferon alpha 2A and ribavirin therapy in patients of chronic hepatitis C

To determine end treatment and sustained virological response to conventional interferon's and ribavirin. This descriptive study was conducted from January 2009 to September 2011 at DHQ hospital Dir, KPK, Pakistan. Three hundred and forty-seven patients of chronic hepatitis C aged 18 to 60 years were given conventional Interferons alpha 2a and Ribavirin for six months under Prime Minister Program for control of hepatitis. Out of three hundred and forty seven patients three hundred and thirty nine patients completed the therapy. End treatment response was achieved in 229[67.5%] patients and sustained virological response was seen in 210[61.94%] patients. Combination of conventional interferon and ribavirin has a high sustained virological response with fewer side effects in our study. In resource depleted countries like Pakistan, conventional interferon alpha 2a and ribavirin combination therapy can be used as the first line treatment for non affording chronic hepatitis C patients

Avaliação da presença de mutações de resistência no gene da NS5B e do prognóstico da infecção pelo HCV através da IL-28B em pacientes monoinfectados com HCV no RJ / Evaluation of resistance mutations presence in the NS5B gene and prognosis of HCV infection throught IL-28B in HCV monoinfected patients of RJ

Estima-se que a prevalência global da população mundial com hepatite C é de 3%. Pouco se sabe sobre a resposta ao tratamento com respeito à resistência viral. Algumas mutações no fragmento de 109 aminoácidos da NS5B são associadas com resistência ao interferon (IFN) e ribavirina (RBV). Estudos moleculares e clínicos identificaram fatores associados com o hospedeiro e vírus relacionados associada com a resposta ao tratamento, tal como o gene que codifica a IL-28B. Este estudo foi dividido em duas fases, cujos objetivos foram caracterizar a frequência de mutações que conferem resistência ao HCV e avaliar a relevância das mutações em pacientes Respondedores (R) ou Não Respondedores (NR) ao tratamento e caracterizar geneticamente as populações sobre polimorfismos genéticos nos SNPs da IL-28B em relação ao prognóstico da resposta ao tratamento. As amostras dos pacientes foram submetidas a testes de genotipagem e carga viral. As sequências geradas foram comparadas no BLAST e no banco de dados Los Alamos HCV. Realizamos o alinhamento das sequências homólogas e as mutações identificadas. Com base no genótipo e carga viral determinamos a classificação dos pacientes de acordo com a resposta à terapia. O DNA genômico foi isolado a partir de sangue periférico para a realização da tipagem de SNPs de IL-28B. A metodologia utilizada foi de PCR em tempo real utilizando sondas TaqMan SNP específico. A análise dos dados foi realizada utilizando GraphPad Prism com qui-quadrado, risco relativo (RR), Odds Ratio (OR) e intervalo de confiança de 95%, com um nível de significância de P <0,05. Foi encontrado na primeira fase deste estudo uma taxa significativa mutações associadas ao tratamento nas amostras estudadas. A prevalência de mutações associadas à resistência ao IFN e RBV bem como a novos medicamentos antivirais localizados no fragmento de 109 aminoácidos da NS5B foi examinado em 69 indivíduos infectados naïve no Rio de Janeiro, Brasil. Na segunda fase, as mutações foram ...

It is estimated that the overall prevalence of the average world population with hepatitis C is 3%. Little is known about the treatment response with respect to viral resistance. Some mutations in the 109-aminoacid fragment of NS5B are associated to Interferon (IFN) and Ribavirin (RBV) resistance. Molecular and clinical studies have identified factors associated with the host and related viruses associated with response to treatment, as the gene encoding IL-28B. This study was divided into two phases whose objectives were to characterize the frequency of mutations conferring resistance to HCV viral evaluating the relevance of these in Responders (R) or Non-Responders (NR) patients to treatment and to characterize genetically the populations regarding genetic polymorphisms SNPs IL-28B in relation to prognosis of response to treatment for HCV. Patient samples were subjected to tests for genotyping and viral load. The sequences generated were compared in the BLAST and the Los Alamos database HCV. We conducted the alignment of homologous sequences and mutations identified. Based on virological parameters genotype and viral load determined the classification of patients according to response to therapy. Genomic DNA was isolated from peripheral blood for carrying out the typing of SNPs of IL-28B. The methodology used was real-time PCR using TaqMan probes specific SNPs. Data analysis was performed using GraphPad Prism with chi-square, relative risk (RR), Odds Ratio (OR) and confidence interval of 95% with a significance level of P <0.05. To study these biological parameters we associated the responsive patients, non-responders, the viral load, genotype, and IL-28B polymorphism to treatment outcome. We found in the first phase of this study a significant rate of treatment-associated mutations in the samples studied. The prevalence of mutations associated to resistance to interferon and ribavirin (IFN/RBV) as well new antiviral drugs located in the 109 aminoacid ...

A reduced dose of ribavirin does not influence the virologic response during pegylated interferon alpha-2b and ribavirin combination therapy in patients with genotype 1 chronic hepatitis C

BACKGROUND/AIMS: When combined with pegylated interferon alpha-2b (Peg-IFN alpha-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV. METHODS: We retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg-IFN alpha-2b and RBV combination therapy. We divided the patients into groups A (> or =15 mg/kg/day, n=23) and B (<15 mg/kg/day, n=26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion. RESULTS: The early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, P=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, P=0.01). CONCLUSIONS: RBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients.

Association of hepatitis C virus NS5B variants with resistance to new antiviral drugs among untreated patients

Mutations located in the 109-amino acid fragment of NS5B are typically associated with resistance to interferon (IFN) and ribavirin (RIB) and to new antiviral drugs. The prevalence of these mutations was examined in 69 drug-naïve individuals with hepatitis C virus (HCV) infections in Rio de Janeiro, Brazil. Mutations related to non-response to IFN/RIB were observed in all subtypes studied (1a, 1b, 2b, 3a and 4). The most common mutation was Q309R, present in all subtypes, except subtype 2b with frequency above 20 percent. D244N was detected only in subtype 3a and A333E was detected only in subtype 2b. We did not detect the S282T, S326G or T329I mutations in any of the samples analysed. Of note, the C316N mutation, previously related to a new non-nucleoside compound (HCV796 and AG-021541), was observed in only eight of 33 (24 percent) samples from subtype 1b. Site 316 was under positive selection in this HCV variant. Our data highlight the presence of previously described resistance mutations in HCV genotypes from drug-naïve patients.

Síndrome respiratorio agudo severo (sras): esperando lo impensable / Severe acute respiratory syndrome (sars): waiting for the unthinkable

A comienzos de Febrero de 2003, la Organización Mundial de la Salud comenzó a recibir informes de pacientes co un síndrome caracterizado por una neumonía atípica con una rápida progresión a una insuficiencia respiratoria sin una etiología identificada, a pesar de grandes estudios de diagnóstico. La mayoría de estos informes señalaban que el brote se inició en el Sur de China, específicamente en la provincia de Guandong. El brote inicial en el Sudoeste de Asia ya se ha diseminado a otras regiones en Asia, Europa, Norte y Sud América y Sud Africa. Muchos de estos casos pueden ser relacionados por cadenas de transmisión, de un caso índice procedente de la provincia de Guandong, quien visitaba Hong Kong. Aunque la manera exacta de transmisión no ha sido claramente establecida, la etiología de este síndrome ya ha sido identificada. Una nueva variedad de Coronavirus, ha sido indentificada por microscopía electrónica y estudios moleculares de secreciones respiratorias, en un gran número de laboratorios a través del mundo. El síndrome ha sido definido como SRAS (Sindrome Respiratorio Agudo Severo) por la OMS y se carateriza por un periodo de incubación de 2 a 10 días y por una fase febril que generalmente dura tres días. Durante la fase respiratoria, que comienza alrededor del tercer día, los pacientes presentan síntomas respiratorios, como tos seca, disnea, e hipoxemia. El apoyo ventilatorio es requerido en alrededor de un 14 a un 38 por ciento de los casos y los índices de mortalidad varían entre 0 y un 50 por ciento. Los hallazgos de laboratorio en el SRAS incluyen leucopenia, trombocitopenia y un alza de la transaminasas y de los niveles de deshigrogenasa láctica. El tratamiento del SRAS incluye medidas de apoyo y la utilización empírica de ribavirina. Aislamiento respiratorio por gotitas, uso de máscaras respiratorias y un estricto lavado de manos, constituyen las principales medidas de prevención. La confirmación de un caso debe realizarse en laboratorios de referencia con estudios serológicos y moleculares. Desde el comienzo de la epidemia, Chile (MINSAL ciruclar 31) estableció un sistema de vigilancia, así como también guías clínicas y recomendaciones para la identificación, prevención de casos secundarios y manejo clínico de casos sospechosos

In vitro antiviral activity of bael (Aegle marmelos Corr) upon human coxsackieviruses B1-B6.

The in-vitro antiviral activity of a series of compounds in samples extracted from various parts of the Indian holy tree, Bael (Aegle marmelos corr.) were evaluated for their efficacy against human coxsackieviruses B1-B6. The inhibitory concentrations (IC50) for leaves (L1 and L2) stem and stem bark (S1, S2, S3 and S4) fruit (F1 and F2micro) root and root bark (R1 and R2) and pure compound, the marmelide were 1000 microg/ml (for L1 and L2), 1000 microg/ml (for S1, S2, S3 and S4), 1000 microg/ml (for F1) and 500 microg/ml (for F2) 250 microg/ml (for R1) and 500 microg/ml (for R2) and 62.5 microg/ml for marmelide respectively by plaque inhibition assay at 96 hrs. On the other hand, the corresponding value for Ribavirin, a standard antiviral drug, was 2000 microg/ml for the same viruses at the same time period. These concentrations did not exhibit any toxicity to Vero cells, the host subtoxic concentrations were 5000 microg/ml for leaf and stem fractions 2000 microg/ml for fruit fractions 500 and 1000 microg/ml for root fractions 250 microg/ml for marmelide and 2000 microg/ml for Ribavirin. The cytotoxic concentrations were 8000 microg/ml for leaf and stem compounds 4000 mg/ml for fruit; 1000 microg/ml and 2000 microg/ml for root 500 microg/ml for marmelide and 4000 microg/ml for ribavirin at 96 hrs. These were also confirmed by trypan blue dye exclusion test and further passaging of cells. Additionally pretreatment of host cells, virus inactivation, yield reduction and effect of time of addition assays against coxsackievirus B3 suggested that marmelide was most effective as a virucidal agent besides interfering at early events of its replicative cycle like adsorption, penetration, at various steps in single cycle growth curve and effect of time of addition.

Effect of ribavirin on epididymal sperm count in rat.

Ribavirin (1-beta-D-ribofuranosyl-1, 2, 4-triazole-3-Carboxamide) is a potent inhibitor of inosine monophosphate dehydrogenase, used widely as an antiviral drug. Although it has been reported as a teratogen, its effect on spermatogenesis is not known. Male Wistar rats were segregated into 24 groups of 5 in each. Six groups were treated with water, 6 groups with 20 mg/kg, another 6 groups with 100 mg/kg and remaining 6 groups with 200 mg/kg for 5 days at intervals of 24 h (i.p.). Animals were anaesthetized at 14, 28, 35, 42, 70 and 105 days following the last exposure, laparatomy was conducted, epididymis was removed, minced in 1 ml phosphate buffered saline (PBS, pH 7.2), filtered and stained with 1% aqueous eosin Y. An aliquot was taken in haemocytometer, diluted in PBS and charged into Neubauer's chamber. Spermatozoa were counted in 8 squares except the central, and multiplied by 5 x 10(4). Data were analysed by Mann-Whitney "U" test. Ribavirin significantly decreased the sperm count in a dose and time dependent pattern and showed a recovery by day 105 except at 200 mg/kg. Ribavirin is reversibly cytotoxic to germ cells and decreases the production of spermatozoa.

Tratamiento de la varicela con ribavirina: estudio de efectividad en población abierta / The treatment of the varicella with rivavirin: evaluation on effectiveness

Objetivo. El tratamiento de la varicela ha sido tradicionalmente sintomático, aunque la terapia antiviral se acepta en ciertas condiciones. La evaluación de los tratamientos, en ese caso antivirales, se ha centrado en estudios de eficacia pero no de efectividad, lo cual refleja el valor real en población abierta y no en pacientes estrictamente seleccionados y controlados. Actualmente, se conoce la eficacia de la ribavirina pero no su efectividad, por lo que se consideró importante evaluar este aspecto con el presente estudio abierto. Resultados. En un estudio abierto prospectivo, se incluyeron 494 pacientes pediátricos tratados con ribavirina a dosis de 20 mg/kg/día en tres tomas. El tiempo promedio de evolución fue de 2.6 días. El exantema mostró pocas lesiones y brotes así como el desarrollo a etapa de costra en 69.4 por ciento de los casos en los primeros siete días. La hipertermia, anorexia, irritabilidad y malestar general, mostraron una desaparición rápida y notoria desde los primeros días. Los eventos adversos se presentaron en 9.9 por ciento de los casos, atribuibles a medicación concomitante. A criterio médico la evolución fue más favorable y de menor duración en la mayoría de los casos (97.9 por ciento) en relación a la experiecia previa con otros esquemas de manejo.

Elimination of eggplant mottled crinkle virus using virazole in explant cultures of Solanum melongena L.

Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide; 100 and 150 mg/l) incorporated into brinjal explant culture medium induced in complete elimination of eggplant mottled crinkle virus - Indian isolate (EMCV-1) from infected explant cultures of S. melongena L. and production of virus free plant progeny. Acridine orange and ethidium bromide (150 ml/l) were also potent antiviral agents to some extent.

Antiviral effect of ribavirin on Junin virus replication in vitro

La ribavirina (1-ß-ribofuranosil-1,2,4-triazole-3-carboxamida; Virazole N. R.) es un nucleósido sintético con un amplio espectro de actividad antiviral demostrada en cultivos celulares, en animales experimentales y en ensayos clínicos. Con el objeto de evaluar el efecto de ribavirina en la replicación del virus Junin in vitro se infectaron células Vero a diferentes multiplicidades de infeccíon con la cepa atenuada XJCL3- y luego de 1 h de adsorción se agregó medio de cultivo conteniendo diferentes concentraciones de la droga (desde 3,12 a 100 microng/ml). Los parámetros medidos fueron los seguientes: 1) Inhibición de la acción citopatogénica a diferentes períodos post-infección. 2) Reducción de la producción viral mediante titulación de unidades formadoras de placas en los sobrenadantes de los cultivos al quinto día post-infección. 3) Inhibición de la formación de placas bajo medio semisólido conteniendo diferentes concentraciones del fármaco. 4) Cantidad relativa de antígeno producida por las células infectadas en presencia del quimioterápico mediante un enzimo-inmunoensayo. Se observó que una concentración de la droga de 3,12 microng/ml inhibe la acción citopatogénica presente al quinto día post-infección en cultivos no tratados mientras que concentraciones de 25 microng/ml reducen a niveles no detectables por los métodos utilizados la producción viral (Figura 1), la formación de placas (Figura 2) y la síntesis de proteínas virales (Figura 3). Estos hallazgos, sumados a la baja toxicidad observada en ensayos clínicos con ribavirina en pacientes con Fiebre de Lassa indicaron la necesidad de realizar pruebas en primates infectados con virus Junin