Exantema en enfermedad por virus de inmunodeficiencia humana, ¿manifestación de infección o reacción alérgica?

Paciente varón que presentó exantema maculopapular, no pruriginoso, sin afectación palmoplantar, luego de recibir tratamiento con trimetoprim/sulfametoxazol por siete días debido a sintomatología gastrointestinal. Tras realizar historia clínica completa y con pruebas de cuarta generación se confirmó infección por VIH. Al quinto día de tratamiento antirretroviral presentó nuevas lesiones eritematosas con descamación gruesa, pruriginosas, edema facial y eosinofilia. Se realizó una biopsia de piel que reportó una dermatitis liquenoide, con espongiosis, degeneración vacuolar de la capa basal, queratinocitos necróticos e infiltrado de eosinófilos, características que favorecen la reacción por drogas. El tratamiento consistió en interrumpir la terapia combinada, uso de corticoides sistémicos, antihistamínicos y ya que, no se trató de un cuadro severo, se reinició el tratamiento antirretroviral sin complicaciones.

A male patient presented with a maculopapular, non-pruritic rash, without palmoplantar involvement, after receiving treatment with trimethoprim/sulfamethoxazole for seven days due to gastrointestinal symptoms. After taking a complete medical history and using fourth-generation tests confirmed HIV infection. On the fifth day of antiretroviral treatment, he presented new erythematous lesions with thick, pruritic scaling, facial edema and eosinophilia. A skin biopsy reported lichenoid dermatitis, with spongiosis, vacuolar degeneration of the basal layer, necrotic keratinocytes and eosinophil infiltrate, characteristics that favor drug reaction. The treatment consisted of interrupting the combined therapy, using systemic corticosteroids, antihistamines and since it was not a severe condition, antiretroviral treatment restarted without complications.

Predictive factors for functional cure after sequential therapy with nucleos(t)ide analogues and pegylated interferon alfa-2b in treatment of chronic hepatitis B / 临床肝胆病杂志

Objective To investigate the independent predictive factors for functional cure after long-term nucleos(t)ide analogue (NUC) antiviral therapy followed by pegylated interferon α-2b therapy in chronic hepatitis B (CHB) patients. Methods A total of 162 CHB patients who were admitted to several hospitals in Qingdao, China, from 2018 to 2021 were enrolled as subjects, and all patients received pegylated interferon α-2b for at least 48 weeks after NUC therapy for one year or longer. According to whether HBsAg clearance was achieved at week 48 of pegylated interferon α-2b treatment, the patients were divided into functional cure group with 79 patients and non-cure group with 83 patients, and related clinical indices were compared between the two groups. The two-independent-samples t test and the Mann-Whitney U rank sum test were used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation analysis was performed, and the univariate and multivariate logistic regression analyses were used to investigate the independent predictive factors for functional cure. The receiver operating characteristic (ROC) curve was plotted for related variables, and the area under the ROC curve (AUC) was used to evaluate the prediction accuracy of the variables. Results Compared with the non-cure group, the functional cure group had a significantly lower HBsAg level at baseline [21.63 (3.33-157.60) IU/mL vs 794.70 (336.10-1 185.34) IU/mL, Z =-8.869, P 1000 IU/mL (0 vs 8.4%, χ 2 =5.073, P =0.024), a significantly lower level of total bilirubin at baseline [12.60 (10.12-15.93) μmol/L vs 15.50 (11.80-24.10) μmol/L, Z =-3.611, P 2×upper limit of normal (16.5% vs 4.8%, χ 2 =5.835, P =0.016). The multivariate logistic regression analysis showed that baseline HBsAg (odds ratio [ OR ]=0.996, 95% confidence interval [ CI ]: 0.995-0.997, P < 0.001), HBsAg at week 12 of pegylated interferon α-2b treatment ( OR =0.990, 95% CI : 0.986-0.994, P < 0.001), HBsAg at week 24 of pegylated interferon α-2b treatment ( OR =0.983, 95% CI : 0.975-0.991, P < 0.001), and baseline total bilirubin ( OR =0.885, 95% CI : 0.826-0.949, P =0.001) were independent predictive factors for functional cure. The ROC curve of baseline HBsAg showed an AUC of 0.904 and the optimal cut-off value of 118.24 IU/mL; the ROC curve of HBsAg at week 12 of pegylated interferon α-2b treatment showed an AUC of 0.948 and the optimal cut-off value of 73.74 IU/mL; the ROC curve of HBsAg at week 24 of pegylated interferon α-2b treatment showed an AUC of 0.975 and the optimal cut-off value of 11.01 IU/mL; the ROC curve of baseline total bilirubin showed an AUC of 0.664 and the optimal cut-off value of 19.9 μmol/L. Conclusion Baseline HBsAg, HBsAg at week 12 of pegylated interferon α-2b treatment, HBsAg at week 24 of pegylated interferon α-2b, and baseline total bilirubin are independent predictive factors for functional cure at week 48 of pegylated interferon α-2b treatment in CHB patients receiving sequential therapy with NUC and pegylated interferon α-2b.

Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C / 中华肝脏病杂志

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.

Caracterización de pacientes con hepatitis C que recibieron tratamiento con drogas antivirales de acción directa

Introducción: La hepatitis C constituye un problema de salud pública mundial por su prevalencia y progresión a la cronicidad. El tratamiento de la hepatitis C con drogas antivirales de acción directa ha revolucionado la práctica de la hepatología clínica por la posibilidad de curar a la mayoría de los pacientes con tratamientos cortos y sin efectos adversos significativos. Objetivo: Caracterizar los pacientes con hepatitis C que recibieron tratamiento con drogas antivirales de acción directa en la provincia Camagüey. Métodos: Se realizó un estudio observacional descriptivo, transversal y retrospectivo en la provincia Camagüey durante el período del 4 de enero del año 2021 al 28 de marzo del año 2022. El universo de estudio estuvo constituido por 405 pacientes con diagnóstico de hepatitis C en la provincia. La muestra por 110 pacientes que hicieron tratamiento con ribavirina e interferón pegilado y no resolvieron pues sus cargas siguió detectables. Resultados: Se observó un predominio de los pacientes con hepatitis C en el grupo de edad de 55-59 años, sexo masculino, con 1 a 3 años de diagnosticada la enfermedad. No todos terminaron el tratamiento debido a la ocurrencia de fallecimientos. Los que cumplieron con el uso de las drogas antivirales de acción directa sofosbuvir y daclatasvir durante las 12 semanas, en su gran mayoría sus cargas virales resultaron no detectables fundamentalmente en población, no así en los hemodializados aunque estos disminuyeron sus cifras con relación a las que tenían antes de iniciar el tratamiento. Conclusiones: El tratamiento resultó ser efectivo.

Introduction: Hepatitis C constitutes a global public health problem due to its prevalence and progression to chronicity. The treatment of hepatitis C with direct-acting antiviral drugs has revolutionized the practice of clinical hepatology due to the possibility of curing the majority of patients with short treatments and without significant side effects. Objective: To characterize patients with hepatitis C who received treatment with direct-acting antiviral drugs in Camagüey province. Methods: A descriptive, cross-sectional and retrospective observational study was carried out in the Camagüey province during the period from January 4th, 2021 to March 28th, 2022. The universe of study consisted of 405 patients diagnosed with hepatitis C in the province. The sample was made up of 110 patients who underwent treatment with ribavirin and pegylated interferon and did not resolve as their charges continued to be detectable. Results: A predominance of patients with hepatitis C was observed in the age group of 55-59 years, male, with 1 to 3 years of diagnosis of the disease. Not all patients completed treatment due to the occurrence of deaths. Those who complied with the use of the direct-acting antiviral drugs sofosbuvir and daclatasvir during the 12 weeks, the vast majority of their viral loads were not detectable, mainly in the population, not so in the hemodialysis patients, although their figures decreased in relation to those who they had before starting treatment. Conclusions: The treatment turned out to be effective.

Effectiveness of wearing masks during the COVID-19 outbreak in cohort and case-control studies: a systematic review and meta-analysis / Eficácia do uso de máscaras durante o surto de COVID-19 em estudos de coorte e caso-controle: uma revisão sistemática e meta-análise

ABSTRACT Objective: To evaluate the efficacy of wearing a mask to prevent COVID-19 infection. Methods: This was a systematic review and meta-analysis of cohort and case-control studies, considering the best level of evidence available. Electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov) were searched to identify studies that evaluated the effectiveness of wearing masks compared with that of not wearing them during the COVID-19 pandemic. Risk of bias and quality of evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation. Results: Of the 1,028 studies identified, 9 met the inclusion criteria (2 cohort studies and 7 case-control studies) and were included in the analysis. The meta-analysis using cohort studies alone showed statistically significant differences, wearing a cloth mask decreased by 21% [RD = −0.21 (95% CI, −0.34 to −0.07); I2 = 0%; p = 0,002] the risk of COVID-19 infection, but the quality of evidence was low. Regarding case-control studies, wearing a surgical mask reduced the chance of COVID-19 infection [OR = 0.51 (95% CI, 0.37-0.70); I2 = 47%; p = 0.0001], as did wearing an N95 respirator mask [OR = 0.31 (95% CI, 0.20-0.49); I2 = 0%; p = 0.00001], both with low quality of evidence. Conclusions: In this systematic review with meta-analysis, we showed the effectiveness of wearing masks in the prevention of SARS-CoV-2 infection regardless of the type of mask (disposable surgical mask, common masks, including cloth masks, or N95 respirators), although the studies evaluated presented with low quality of evidence and important biases.

RESUMO Objetivo: Avaliar a eficácia do uso de máscaras na prevenção da infecção por COVID-19. Métodos: Revisão sistemática e meta-análise de estudos de coorte e caso-controle, considerando o melhor nível de evidência disponível. Bancos de dados eletrônicos (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials e ClinicalTrials.gov) foram pesquisados para identificar estudos que avaliassem a eficácia do uso de máscaras em comparação com ausência de seu uso durante a pandemia de COVID-19. O risco de viés e a qualidade da evidência foram avaliados usando a ferramenta Cochrane risk of bias e Grading of Recommendations Assessment, Development, and Evaluation. Resultados: Dos 1.028 estudos identificados, 9 preencheram os critérios de inclusão (2 estudos de coorte e 7 estudos de caso-controle) e foram incluídos na análise. A meta-análise usando apenas estudos de coorte mostrou diferenças estatisticamente significativas: o uso de máscara de tecido diminuiu 21% [(risk difference = −0,21 (IC 95%: −0,34 a −0,07); I2 = 0%; p = 0,002] o risco de infecção por COVID-19, mas a qualidade da evidência foi baixa. Em relação aos estudos caso-controle, o uso de máscara cirúrgica reduziu a chance de infecção por COVID-19 [OR = 0,51 (IC 95%: 0,37-0,70); I2 = 47%; p = 0,0001], assim como o uso de máscara respiratória N95 [OR = 0,31 (IC 95%: 0,20-0,49); I2 = 0%; p = 0,00001], ambos com baixa qualidade de evidência. Conclusões: Nesta revisão sistemática com meta-análise, demonstramos a eficácia do uso de máscaras na prevenção da infecção por SARS-CoV-2 independentemente do tipo de máscara (máscara cirúrgica descartável, máscaras comuns, incluindo máscaras de tecido, ou respiradores N95), embora os estudos avaliados apresentassem evidências de baixa qualidade e vieses importantes.

Reasonable selection of antiviral agents for herpes zoster / 中华皮肤科杂志

Antiviral treatment is the core part in the treatment of herpes zoster. Based on the latest studies, consensus and guidelines, this article aims to provide a basis and reference for clinicians to make a reasonable choice of types and doses of antiviral agents. Valacyclovir, a precursor of acyclovir with high oral bioavailability and great convenience of administration, is generally the first choice of oral antiviral agents; for some special cases, such as immunocompromised patients, intravenous drips of acyclovir should be selected when appropriate. Brivudine is often a better choice for patients with severe renal insufficiency; famciclovir or other antiviral agents should be considered for patients resistant to acyclovir; for immunocompromised patients resistant to acyclovir, intravenous drips of foscarnet sodium can be an option. Oral antiviral agents should be administered at adequate doses. Selecting appropriate antiviral agents and their doses can effectively relieve acute symptoms of patients and reduce the probability of postherpetic neuralgia.

Research advances in antiviral drugs for the treatment of hepatitis D / 临床肝胆病杂志

Hepatitis D virus (HDV) is a satellite virus of hepatitis B virus (HBV) and needs the help of HBV envelope protein to complete its own assembly and replication and then establish a new infection cycle. Chronic HDV infection is considered the most severe form of viral hepatitis, which can accelerate disease progression and increase the risk of liver cancer. Effective antiviral therapy is urgently needed to delay disease progression in patients with HDV infection, but Bulevirtide conditionally approved by European Medicines Agency in July 2020 and interferon previously recommended are the only drugs used for the treatment of HDV infection. At present, studies are being conducted for several antiviral drugs targeting viral replication cycle, and early clinical trials have obtained good results. This means that important breakthroughs have been made in the development of antiviral drugs, bringing hope for the treatment of hepatitis D. This article summarizes the current antiviral drugs for hepatitis D and discusses related treatment regimens, so as to provide a reference for the treatment of hepatitis D.

Access to antiviral therapy for chronic hepatitis B during COVID-19

Abstract OBJECTIVE: Hepatitis B is an important public health concern. Currently, the COVID-19 pandemic is a major challenge for health systems, and the access to pharmacologic and non-pharmacologic treatment of chronic diseases, such as hepatitis B, may have been affected due to the contingency measures. This study aimed to evaluate the access to antiviral therapy during the ongoing pandemic. METHODS: This was a descriptive analysis of the access to treatment for chronic hepatitis B at a tertiary-level university hospital in São Paulo, integrated with the Brazilian health system. The study was conducted from April to December 2020. RESULTS: Access to antiviral therapy for 225 patients was assessed. The majority of the population was male (59%). The main type of service was the Programa Medicamento em Casa (Home Medication Delivery Program), which was availed by 144 (64%) patients. Women had poorer access to antiviral therapy (56%, p<0.05), and patients registered in the HMDP (68%, p<0.05) had better access. The age group of >48 years represented 70% of the group without access to antiviral therapy. Twenty-two pharmaceutical appointments were conducted through phone calls with patients without access to antiviral therapy. CONCLUSION: This study contributes to the rationalization of efforts in a public health crisis through the identification of groups with the highest risk of poor access to antiviral therapy and the demonstration of the benefits of a medication delivery system.

Treatment of Hepatitis C with Direct-Acting Antivirals does not Induce Significant Arrhythmias

Abstract Background Chronic Hepatitis C (CHC) therapy with direct-acting antivirals (DAAs) has high efficacy and safety, but some cases of bradyarrhythmias have been described. Objective To evaluate heart rhythm disorders during DAA treatments. Methods Forty-eight patients with CHC (mean 61 years of age; 56% males; 73% HCV genotype 1) were evaluated before and during treatment with DAAs, analyzed by a resting 12-lead ECG [PR, QRS, and QT corrected (QTc) intervals measured] and a 24-h-Holter system, to evaluate the heart rate (HR) and the occurrence of arrhythmias. The Student's t-test or the Wilcoxon-Mann-Whitney test for continuous, independent variables were performed with a statistically significant p-value < 0.05. Results The electrocardiographic parameters before and during treatment were: PR interval (147.2 ± 15.6 vs 144.9 ± 15.6 ms; p = 0.21), QTc interval (427 ± 22.3 vs 421.7 ± 25.3 ms; p = 0.24), minimum HR (52.7 ± 8.4 vs 53.2 ± 8.5 bpm; p = 0.49), median HR (74.2 ± 10.4 vs 75.2 ± 9 bpm; p = 0.83), and maximum HR (117.4 ± 16.8 vs 117.9 ± 16.3 bpm; p = 0.25). These parameters proved to be similar among 11 beta-blockers or 22 ribavirin users. During treatment, the 21 cirrhotic patients presented significantly lower median HRs (72.1 ± 9.0 vs 77.9 ± 8.2 bpm; p = 0.02) and maximum HRs (108.9 ± 15.2 vs. 125.1 ± 13.2 bpm, p < 0.0001) through a 24-h-Holter monitoring than the patients without cirrhosis. No clinically relevant arrhythmias were detected. Conclusion DAAs do not significantly influence heart rate or induce significant cardiac arrhythmias in patients with CHC.

Uso profiláctico de nasalferon contra la COVID-19 en trabajadores de la salud. Estudio de vigilancia temprana / Prophylactic use of nasalferon against COVID-19 in healthcare workers. Early surveillance stud

RESUMEN Introducción: En Cuba se empezó la aplicación nasal de IFN alfa 2b recombinante humano (Nasalferon) en personal de riesgo para prevenir la infección por el SARS-CoV-2. Objetivo: caracterizar la seguridad de los expuestos al uso del Nasalferon en el Centro de Investigaciones Médico Quirúrgicas y explorar el efecto del uso profiláctico del fármaco contra cuadros respiratorios agudos causados preferentemente por el SARS-CoV-2. Material y Métodos: Estudio epidemiológico monocéntrico, prospectivo, abierto, de vigilancia temprana en trabajadores sanitarios, a los que se le administró nasalferon. Se realizó la vigilancia mediante el método de Vigilancia del Monitoreo de Eventos Adversos Ligados a la Prescripción. La variable principal fue la presencia de eventos adversos. Secundariamente se exploró el efecto del fármaco en la prevención de infección por el virus. Para el análisis de la variable principal se estimó la proporción de sujetos con cada uno de los eventos adversos que se presentaron. Se estimaron, además, la distribución de frecuencia del tipo de evento, intensidad, gravedad y la causalidad o imputabilidad. Resultados: Se incluyeron 86 sujetos, de ellos, 50 experimentaron 15 tipos de eventos adversos. No se reportaron eventos severos ni graves. Los catalogados como moderados fueron: cefalea, leucopenia, decaimiento e hipertensión arterial. Durante el tiempo que duró el tratamiento y hasta un mes después de este, ninguno de los sujetos incluidos presentó COVID-19 ni otros cuadros respiratorios agudos virales. Conclusiones: El Nasalferon resultó ser un fármaco seguro y tolerable y los sujetos incluidos no presentaron cuadros respiratorios agudos relacionados o no con la COVID-19.

ABSTRACT Introduction: In Cuba, the nasal application of recombinant human IFN-alpha- 2b (nasalferon) began in personnel at risk in order to prevent SARS-CoV-2 infection. Objective: To characterize the safety in those subjects exposed to the use of Nasalferon at the Surgical Medical Research Center and to explore the effect of the prophylactic use of the drug against acute respiratory symptoms mainly caused by SARS-CoV-2. Material and Methods: Monocentric, prospective, open, and early surveillance epidemiological study conducted in healthcare workers who were administered Nasalferon. Surveillance was performed using the Prescription-Related Adverse Event Monitoring Surveillance method. The main variable was the presence of adverse events. Secondarily, the effect of the drug in preventing virus infection was explored. For the analysis of the main variable, the proportion of subjects who experienced each of the adverse events was estimated. In addition, the frequency distribution of the type of event, intensity, severity, and causality or imputability were estimated. Results: A total of 86 subjects were included; 50 of them experienced 15 types of adverse events. No severe or serious events were reported. Headache, leukopenia, decay, and arterial hypertension were classified as moderate ones. During the whole duration of the treatment and until a month after it, none of the subjects included in the study presented COVID-19 or other viral acute respiratory symptoms. Conclusions: Nasalferon proved to be a safe and tolerable drug and the included subjects did not present acute respiratory symptoms related or unrelated to COVID-19.

Antivirais para pacientes adultos hospitalizados com infecção por SARS-CoV-2: Um estudo de Fase II/III, randomizado, multicêntrico, controlado por placebo, adaptativo, com múltiplos braços e estágios. COALITION COVID-19 BRAZIL IX - REVOLUTIOn: protocolo e plano de análise estatística / Antivirals for adult patients hospitalized with SARS-CoV-2 infection: A randomized, Phase II/III, multicenter, placebo-controlled, adaptive study, with multiple arms and stages. COALITION COVID-19 BRAZIL IX - REVOLUTIOn: protocol and statistical analysis plan

RESUMO Os medicamentos reaproveitados são importantes em contextos de recursos limitados porque as intervenções estão mais rapidamente disponíveis, já foram testadas com segurança em outras populações e são, em geral, mais baratas. Os medicamentos reaproveitados são uma solução eficaz, especialmente para doenças emergentes, como a COVID-19. O estudo REVOLUTIOn visa avaliar três medicamentos antivirais reaproveitados: atazanavir, daclatasvir e sofosbuvir, já utilizados em pacientes infectados pelo HIV ou pelo vírus da hepatite C, em um estudo randomizado, controlado por placebo, adaptativo, multibraço e em múltiplos estágios. Os medicamentos serão testados simultaneamente em um ensaio de Fase II para primeiro identificar se algum deles, isoladamente ou em combinação, reduz a carga viral. Se reduzirem, será iniciado um estudo de Fase III para investigar se tais medicamentos são capazes de aumentar o número de dias sem suporte respiratório. Os participantes devem ser adultos hospitalizados com idade ≥ 18 anos com início dos sintomas ≤ 9 dias e saturação de oxigênio ≤ 94% em ar ambiente ou necessidade de oxigênio suplementar para manter saturação de oxigênio > 94%. O tamanho total esperado da amostra varia entre 252 e 1.005 participantes, dependendo do número de estágios que serão concluídos no estudo. Assim, o protocolo é aqui descrito em detalhes, juntamente do plano de análise estatística. Em conclusão, o estudo REVOLUTIOn foi concebido para fornecer evidências se o atazanavir, o daclatasvir ou o sofosbuvir reduzem a carga viral de SARS-CoV-2 em pacientes com COVID-19 e aumentam o número de dias em que os pacientes ficam sem suporte respiratório. Neste artigo de protocolo, descrevem-se a fundamentação, o desenho e a situação do ensaio. Identificador do ClinicalTrials.gov:NCT04468087

ABSTRACT Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial. ClinicalTrials.gov identifier:NCT04468087

In vitro antiviral activity against SARS-CoV-2 of plant extracts used in Colombian traditional medicine / Actividad antiviral in vitro contra el SARS-CoV-2 de extractos de plantas usados en medicina tradicional colombiana

Background: Coronavirus infectious disease 2019 (COVID-19) caused by the infection with the new coronavirus SARS-CoV-2 has affected the life and health of more than 222 million people. In the absence of any specific pharmacological treatment, the need to find new therapeutic alternatives is clear. Medicinal plants are widely used worldwide to treat different conditions, including COVID-19; however, in most cases, there are no specific studies to evaluate the efficacy of these treatments. Objective: This article evaluates the antiviral effect of six plant extracts used by indigenous and afro Colombian people against SARS-CoV-2 in vitro. Methods: The antiviral effect of six extracts prepared from plants used in Colombian traditional medicine was evaluated against SARS-CoV-2 through a pre-post treatment strategy on the Vero E6 cell line. Once cytotoxicity was established through an MTT assay, the antiviral effect of the extracts was calculated based on the reduction in the viral titer determined by plaque assay. Results:Gliricidia sepium inhibited SARS-CoV-2 in a 75.6%, 56.8%, 62.5% and 40.0% at 10 mg/mL, 8 mg/mL, 6 mg/mL, and 2 mg/mL, respectively, while Piper tuberculatumtreatment reduced viral titer in 33.3% at 6 mg/mL after 48h. Conclusion:G. sepium and P. tuberculatum extracts exhibit antiviral activity against SARS-CoV-2 in vitro

Introducción: La enfermedad infecciosa causada por el coronavirus 2019 (COVID-19) generada por la infección con el nuevo coronavirus SARS-CoV-2 ha afectado la vida y la salud de mas de 222 millones de personas. En ausencia de algún tratamiento farmacológico específico, la necesidad de encontrar nuevas alternativas terapéuticas es clara. Las plantas medicinales son utilizadas en todo el mundo para tratar diferentes condiciones, incluyendo el COVID-19; sin embargo, en la mayoría de los casos no existen estudios específicos que evalúen la eficacia de estos tratamientos. Objetivo: En este artículo, evaluamos el efecto antiviral de seis extractos de plantas usadas por pueblos indígenas y afrocolombianos contra el SARS-CoV-2 in vitro.Metodología: El efecto antiviral de seis extractos preparados a partir de plantas usadas en medicina tradicional colombiana fue evaluado contra SARS-CoV-2 por medio de una estrategia de pre-post tratamiento en células Vero E6. Una vez se estableció la citotoxicidad por un ensayo de MTT, el efecto antiviral de estos extractos fue calculado basado en la reducción del título viral determinado por ensayo de plaqueo. Resultados:G. sepium inhibió SARS-CoV-2 en un 75.6%, 56.8%, 62.5% y 40.0% a 10 mg/mL, 8 mg/mL, 6 mg/mL, and 2 mg/mL, respectivamente. Mientras el extracto de Piper tuberculatum redujo el título viral en un 33.3% a 6 mg/mL luego de 48h de tratamiento

Tratamiento simplificado para pacientes con Hepatitis C / Simplified treatment for hepatitis C patients

El nuevo tratamiento simplificado con antivirales orales para pacientes con Hepatitis C puede ser abordado desde la atención primaria, lo que facilita el acceso de la población afectada por esta infección crónica. En este artículo se repasan los aspectos claves del diagnóstico, el esquema de tratamiento simplificado y los candidatos a recibirlo. (AU)

The new simplified treatment with oral antivirals for hepatitis C patients can be approached at the primary care level, facilitating access for the population affected by this chronic infection. This article reviews the key aspects of the diagnosis, the simplified treatment scheme, and the eligible candidates for the treatment. (AU)

Tratamento farmacológico para Hepatite C: a incorporação dos antivirais de ação direta pelo Sistema Único de Saúde de 2012 a 2021 / Pharmacological treatment for Hepatitis C: the incorporation of direct-acting by the Unified Health System from 2012 to 2021

A erradicação do vírus da hepatite C (HCV), por meio de tratamento farmacológico, é a única intervenção que pode deter a progressão dessa doença. Os antivirais de ação direta (AAD) de segunda geração respondem por altas taxas de cura em terapias seguras e totalmente orais. No Brasil, diferentes AAD vêm sendo ofertados no Sistema Único de Saúde (SUS), a partir das recomendações da Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde (CONITEC) e mediante critérios de inclusão do Protocolo Clínico e Diretrizes Terapêuticas (PCDT) para hepatite C. Essa dissertação tem como objetivo analisar a dinâmica de incorporação e a efetividade da oferta dos AAD para tratamento da hepatite C no SUS, de 2012 a 2021. Foram realizadas análises documentais dos relatórios de recomendação da CONITEC e das atualizações de PCDT, além de busca nos bancos de dados do Ministério da Saúde sobre compras federais e sobre a dispensação dos medicamentos incorporados na produção ambulatorial do SUS. Dez tratamentos antivirais, compreendendo quinze AAD, foram incorporados ao SUS e, dentre eles, quatro tratamentos antivirais foram posteriormente excluídos no período estudado. Os AAD foram rapidamente demandados à CONITEC para análise de incorporação logo após seus registros na Agência Nacional de Vigilância Sanitária (ANVISA), sendo todos de comercialização global recente e com pouca experiência acumulada de uso. O tempo de conclusão do processo administrativo da CONITEC foi sempre inferior ao prazo máximo legal, com tempo de consulta pública abreviado algumas vezes e sem audiência pública. Essa celeridade, entretanto, esbarra no intervalo entre a incorporação dos AAD e a primeira dispensação no SUS, com média de tempo maior que o prazo legal para a oferta na rede de atenção. Em diversas situações, atrasos na primeira compra pública regular efetuada pelo Ministério da Saúde contribuíram para esses prazos. Incorporada em 2018 e presente no PCDT vigente, a associação elbasvir/grazoprevir não possui registros de compra ou dispensação, conferindo uma situação em que as alternativas terapêuticas permanecem incorporadas e poderiam participar de futuras negociações de preço, conforme critérios de custo-minimização ou de simplificação do tratamento por capacidade pangenotípica. Sinaliza-se que a dinâmica de incorporação e exclusão dos AAD, embora baseada em critérios científicos, pode admitir outras interferências, sejam financeiras ou políticas. O tratamento tornou-se mais simples a partir dos tratamentos pangenotípicos e o país pôde passar a dispensar os AAD na rede de atenção primária, com vistas a melhorar questões de acesso universal ao tratamento.

Eradication of hepatitis C virus (HCV) through pharmacological treatment is the only intervention that can halt the progression of hepatitis C. Second-generation direct-acting antivirals (DAA) account for high cure rates in safe therapies and fully oral. In Brazil, different DAA have been offered in the Unified Health System (SUS), based on the recommendations of the National Commission for the Incorporation of Technologies in the Unified Health System (CONITEC) and through the inclusion criteria of the Clinical Protocol and Therapeutic Guidelines (PCDT) for hepatitis C. This dissertation aims to analyze the dynamics of incorporation and the effectiveness of the offer of DAA for the treatment of hepatitis C in the SUS, from 2012 to 2021. Documentary analyzes of the CONITEC recommendation reports and the PCDT updates were carried out, in addition to a search in the Ministry of Health databases on federal purchases and on the dispensing of medicines incorporated in he SUS outpatient production. Ten antiviral treatments, comprising fifteen DAA, were incorporated into the SUS and, among them, four antiviral treatments were excluded during the study period. The DAA were quickly requested to CONITEC for analysis of incorporation soon after their registration with the National Agency for Sanitary Surveillance (ANVISA), all of them being very recent global marketing and with little accumulated experience of use. The time taken to complete the CONITEC administrative process was always shorter than the maximum legal deadline, with public consultation time shortened a few times and without a public hearing. This speed, however, comes up against the interval between the incorporation of the DAA and the first dispensation in the SUS, with an average time longer than the legal deadline for offering them in the care network. In several situations, delays in the first regular public purchase made by the Ministry of Health contributed to these deadlines. Incorporated in 2018 and present in the current PCDT, the elbasvir/grazoprevir association does not have purchase or dispensing records, giving a situation in which therapeutic alternatives remain incorporated and could participate in future price negotiations, according to cost-minimization or simplification criteria of treatment by pangenotypic capacity. It is pointed out that the dynamics of incorporation and exclusion of DAA, although based on scientific criteria, can admit other interferences, whether financial or political. Treatment became simpler with pangenotypic treatments and the country was able to start to dispense DAA in the primary care network, improving universal access to treatment.

Use of remdesivir in patients with COVID-19: a systematic review and meta-analysis / Uso de remdesivir em pacientes com COVID-19: revisão sistemática e meta-análise

ABSTRACT Objective: Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19. Methods: This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls. Results: A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = −0.01 (95% CI, −0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, −0.08 to 0.01]; p = 0.09). Conclusions: The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.

RESUMO Objetivo: Estudos na literatura sobre o uso de remdesivir no tratamento de pacientes com COVID-19 têm apresentado resultados divergentes. O objetivo deste estudo foi responder a perguntas a respeito do uso de remdesivir no tratamento de pacientes hospitalizados com COVID-19 moderada a grave. Métodos: Trata-se de uma revisão sistemática e meta-análise de ensaios clínicos controlados randomizados (ECR) de fase 3 e estudos observacionais de coorte recuperados de diversos bancos de dados, comparando pacientes hospitalizados com COVID-19 moderada a grave recebendo remdesivir a controles. Resultados: Foram recuperados 207 estudos, dos quais 9 preencheram os critérios de elegibilidade e foram incluídos no estudo. A meta-análise somente dos ECR não mostrou diferenças estatisticamente significativas entre os grupos remdesivir e controle quanto à mortalidade ou ao uso de ventilação mecânica/oxigenação por membrana extracorpórea, e a qualidade das evidências foi moderada e baixa, respectivamente. O uso de remdesivir aumentou a taxa de recuperação em 6% (IC95%: 3-9; p = 0,004) e a taxa de melhora clínica em 7% (IC95%: 1-14; p = 0,02). Além disso, não foram observadas diferenças significativas entre os grupos remdesivir e controle quanto à mortalidade quando a meta-análise concentrou-se apenas nos estudos observacionais de coorte [diferença de risco = −0,01 (IC95%: −0,02 a 0,01); p = 0,32; qualidade das evidências: moderada], e o risco de eventos adversos foi de 4% (IC95%: −0,08 a 0,01; p = 0,09). Conclusões: O uso de remdesivir no tratamento de pacientes com COVID-19 moderada a grave não teve impacto significativo em desfechos clinicamente importantes.

Selection dynamics of HCV genotype 3 resistance-associated substitutions under direct-acting antiviral therapy pressure

ABSTRACT The chronic hepatitis C (CHC) treatment is currently based on the use of direct-acting antivirals (DAAs), and patients infected with hepatitis C virus genotype 3 (GT3) have emerged as a more difficult-to-cure population. The NS5A inhibitor daclatasvir (DCV) and sofosbuvir (SOF), an NS5B viral polymerase inhibitor, are among the drugs that compose more effective and safer treatment regimens. The virus genetic variability is related to resistance-associated substitutions (RASs) that adversely impact DAAs effectiveness. The aims of this study were to analyze the association of NS5A and NS5B RASs and other clinical factors with DAAs regimens effectiveness in patients with GT3 CHC infection. This was a prospective cohort study performed in a Brazilian university hospital. Individuals older than 18 years with GT3 CHC treated with SOF + DCV ± ribavirin (RBV) or SOF + peginterferon (PEG) + RBV were included. Blood samples were collected at baseline and post-treatment. A total of 121 patients were included. Sustained virological response rates were 87.6% for the SOF + DCV ± RBV group and 80.0% for the SOF + PEG + RBV arm. Cirrhosis, prior treatment with interferon/PEG + RBV, and baseline NS5A RAS were associated with higher risk of treatment failure. The NS5A analysis suggested that A30K, Y93H, and RAS at site 62 were related to failure. Interestingly, a likely compensatory effect was shown between A30K and A62T. Emergence of Y93H was always associated with RAS at position 62. The RASs dynamics comprehension is an important tool to indicate more effective treatment for GT3 patients.

Chronic mucocutaneous anogenital herpes: series of ten cases and literature review

Abstract Anogenital herpes is one of the most prevalent sexually transmitted infections worldwide. It has several clinical manifestations, from cases of primary herpes infection to recurrent forms, among them chronic mucocutaneous herpes. This presentation is rare, characterized by a duration of more than four weeks, usually associated with immunosuppression and resistance to classic anti-herpetic treatment. The present study presents a series of ten cases of chronic mucocutaneous herpes with a discussion about its clinical, laboratory, and therapeutic aspects.

Clinical effect of direct-acting antiviral agents in treatment of chronic hepatitis C patients with thrombocytopenia / 临床肝胆病杂志

Objective To investigate the clinical effect of direct-acting antiviral agent (DAA) in the treatment of chronic hepatitis C (CHC) patients with thrombocytopenia and its effect on platelet count (PLT). Methods A retrospective analysis was performed for 83 CHC patients with thrombocytopenia (PLT 100×10 9 /L at baseline had a greater increase in PLT( P < 0.05). Conclusion CHC patients with thrombocytopenia have significant improvements in liver function and LSM after receiving DAA treatment and obtaining SVR12, and baseline LSM is an independent predictive factor for PLT elevation. There is a significant increase in PLT from baseline to EOT and SVR12.

Efficacy and safety of using DAAs to treatment the special populations with chronic hepatitis C / 中国热带医学

@#Abstract:Chronic hepatitis C (CHC) is a global health problem, which is prevalent all over the world. China is a low epidemic area. Hepatitis C virus (HCV) is mainly transmitted through blood, and nowadays, intravenous drug addicts are the key population for the prevention and treatment of hepatitis C. HCV has multiple genotypes and gene subtypes, and the distribution of these genotypes and gene subtypes varies significantly among the regions of the world. Nowadays, the treatment of hepatitis C has entered the era of direct-acting antiviral agents, which have high efficacy and safety in the general population. However, when special populations use direct-acting antiviral agents to treatment hepatitis C, we don't know how its efficacy and safety will be. The special populations include children, adolescents, drug users, HCV/HBV co-infected patients, HCV/HIV co-infected patients, and patients who have comorbidity of HCV and chronic kidney disease. This review will discuss the efficacy and safety of using direct-acting antiviral agents to treat hepatitis C in these special populations.

Updated key points of chronic hepatitis B virus infection: developing drugs for treatment issued by the U.S. food and drug administration(clinical part) / 临床肝胆病杂志

In November 2018, the U.S. food and drug administration (FDA) issued guidance for the development of drugs for chronic hepatitis B virus infection (draft for comments) (hereinafter referred to as draft for comments), and in April 2022, the FDA issued Chronic Hepatitis B Virus Infection: Developing Drugs for Treatment, which has been updated with some details based on the Draft for Comments. This guidance further emphasizes the importance of HBsAg clearance in clinical trials, and classifies chronic suppressive therapy into two categories, namely noninferiority (NI) (or superiority) test with nucleos(t)ide analogues as control and add-on superiority trial with nucleos(t)ide analogues as control, and as for the latter, HBV DNA is no longer recommended as a primary endpoint of the trial, which poses a huge challenge to the development of innovative drugs targeting HBV DNA. The new finite duration therapy should aim to eliminate HBsAg and reduce virologic relapse and the risk of liver disease progression during treatment cessation. Reduction in HBsAg from baseline is not recommended as a primary endpoint for phase Ⅲ clinical trials, since the correlation between such reduction and clinical response remains unclear. In addition, this guidance also specifies the duration of treatment cessation and treatment consolidation period and the criteria for withdrawal of nucleos(t)ide analogues.