High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world.

BACKGROUND & AIMS: Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available. METHODS: GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded. RESULTS: A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin. CONCLUSIONS: In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited. LAY SUMMARY: Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.

Use of Tenofovir Alafenamide/Emtricitabine/Elvitegravir-Cobicistat in HIV-Naive Patients with Advanced Disease: GENIS Study.

Objective: The primary endpoint of the study was to determine the proportion of patients with HIV RNA < 50 copies/mL at 48 weeks. Design: Phase IV, multicentric, open-label, single-arm clinical trial of participants recruited in 2018−2019 to evaluate the efficacy and safety of tenofovir alafenamide/emtricitabine/elvitegravir-cobicistat (TAF/FTC/EVG-c) as first-line treatment in HIV-1 infected naïve participants with advanced disease. Methods: Adverse events were graded according to the Division of AIDS scale version 2.0. Quantitative variables were recorded as median and interquartile range, and qualitative variables as absolute number and percentage. T-Student or Wilcoxon tests were used to analyze intragroup differences of the continuous variables. Results: Fifty participants were recruited with a baseline median CD4 lymphocyte count of 116 cells/µL and a viral load of 218,938 copies/mL. The proportion of patients with viral load <50 copies/mL at week 48 was 94% in the per-protocol analysis, with a median time of 1.9 months to achieve it. Three adverse events attributed to the study drug caused trial discontinuation. Conclusions: the use of TAF/FTC/EVG-c in patients with advanced HIV disease in our study demonstrated efficacy comparable to data from pivotal clinical trials with a good safety profile.

An Easy-to-Implement Risk Score for Targeted Hepatitis C Virus Testing in the General Population.

Despite the effectiveness of available treatments, hepatitis C virus (HCV) remains a major public health problem, mainly due to the high percentage of undiagnosed individuals. We aim to create an easy-to-implement risk score to facilitate targeted HCV testing in the general population. This is a substudy derived from a prospective study in primary care in Madrid (Spain). Participants completed a 21-question risk assessment questionnaire, followed by HCV testing for those with at least one positive response and those >50 years of age, even if they did not answer positively. We used the population >50 years of age to fit a logistic regression model to create a score predicting the risk of a positive test result. We then performed a sensitivity analysis by applying the score obtained to the population <50 years of age, to assess its diagnostic accuracy. Data collected from 2,302 participants were included in the analysis. The prevalence of HCV infection was 1.3%. Five items were selected, showing a C-statistic of 0.896, i.e., male sex, Eastern European origin, use of intravenous drugs, self-perceived risk of acquired HCV infection, and past hepatitis or unexplained liver disease. The sensitivity was 98%, and the negative likelihood ratio was 0.05 for participants with scores of 0 (49.8% in our sample), ruling out HCV infection with high probability. We obtained similar estimates in the population <50 years of age. This tool achieved high diagnostic accuracy to target HCV testing. This could help optimize resources when universal screening is not feasible. IMPORTANCE Despite the highly effective treatments currently available, HCV remains one of the major public health problems related to an infectious agent, mainly because a high percentage of individuals remain undiagnosed. Universal screening has been proposed as a way to end this epidemic; however, it is not feasible in all settings due to different implementation barriers. With this work, we aim to collaborate in improving the diagnosis of HCV infection by creating a simple 5-item score that rules out HCV infection with a very high probability. Almost one-half of the participants in our sample did not present any affirmative answers to these questions, and their probability of being infected was close to 0%. This tool could be a useful strategy and could be considered a cost-effective alternative to optimize resources when universal screening is not feasible.

Case report: From monkeypox pharyngitis to myopericarditis and atypical skin lesions.

Background: A global outbreak of the human monkeypox virus (HMPXV), first identified in May 2022, was declared a health emergency of international concern on 23 July 2022. Before the global outbreak, monkeypox cases were mostly confined to central and west African countries, where this virus is prevalent. Close contact, mainly sexual contact, is supposed to be the main route of transmission, and it is remarkable that the incidence is higher in men who have sexual relationships with other men. Case summary: A 40-year-old Caucasian man arrived at the emergency department complaining of oppressive epigastric pain extending to the chest after a diagnosis of pharyngitis, which was suspected to be caused by the human monkeypox virus. Based on the clinical symptoms, physical examination, serum cardiac biomarkers, and electrocardiographic findings, he was diagnosed with myopericarditis. The real-time PCR for human monkeypox in skin lesions, urine, plasma, and the oropharyngeal swab was positive. The peak of troponin I was 20.6 ng/ml, and the electrocardiogram showed an upward concavity in the ST segment in diffuse leads, which was in agreement with the previous diagnosis. The presence of edema, subepicardial, and myocardial late gadolinium enhancement, and increased values on T1 mapping in the cardiac MRI were in agreement with the diagnosis of myopericarditis. Antiviral treatment with tecovirimat was started with excellent tolerability. After 6 days, the patient recovered and was discharged. Discussion: To our knowledge, this is one of the first reported cases of myopericarditis due to human monkeypox infection, which was confirmed by a cardiac MRI following modified Lake Louise criteria. The short span between the onset of the mucocutaneous symptoms and the myocardial damage suggests a pathogenic association. Furthermore, the active viral replication in plasma samples and the negative results on real-time PCR for other viruses support this clinical association.

Human Monkeypox in People With HIV: Transmission, Clinical Features, and Outcome.

We describe the first 25 persons with HIV diagnosed with human monkeypox virus (MPXV) in our hospital in an ongoing outbreak in Spain. Proctitis was the predominant finding in 52%, and MPXV DNA was detected in rectal swabs from 90%. Proctitis and demonstration of MPXV in rectal swabs support the sexual transmission of MPXV.

CD4+:CD8+ T Cell Ratio Normalization and the Development of AIDS Events in People with HIV Starting Antiretroviral Therapy.

We identify factors associated with the normalization of the CD4+:CD8+ T cell ratio among UK Collaborative HIV Cohort study participants, and describe the association of the CD4+ and CD8+ T cell counts and the CD4+:CD8+ T cell ratio, with the risk of new AIDS events among individuals who achieve a suppressed viral load. Participants initiating combination antiretroviral therapy (cART) after 2006 with a CD4+:CD8+ T cell ratio <1, and viral suppression within 6 months were included. Cox proportional hazard models were used to examine associations with ratio normalization (ratio ≥1). Poisson regression models were used to investigate factors associated with the development of AIDS after viral load suppression. A total of 13,178 participants [median age: 37 (interquartile range: 31-44)] were followed for 75,336 person-years. Of the 4,042 (32.9%) who experienced ratio normalization, individuals with a high CD4+ T cell count [>500 vs. ≤200 cells/mm3, adjusted hazard ratio (95% confidence interval): 7.93 (6.97-9.01)], low CD8+ T cell count [>1,150 vs. ≤500 cells/mm3: 0.18 (0.16-0.21)], and low CD4+:CD8+ T cell ratio [>0.8 vs. <0.2: 12.36 (10.41-14.68)] at cART initiation were more likely to experience ratio normalization. Four hundred and nineteen people developed a new AIDS event. Most recent CD4+ T cell count [>500 vs. ≤200 cells/mm3: adjusted rate ratio 0.24 (0.16-0.34)] and CD4+:CD8+ T cell ratio [>0.8 vs. <0.2: 0.33 (0.21-0.52)] were independently associated with a new AIDS event. One third of study participants experienced ratio normalization after starting cART. CD4+ T cell count and CD4+:CD8+ T cell ratio are both individually associated with ratio normalization and the development of new AIDS events after cART.

Prevalence of HCV infection in a health area of Madrid (Spain): The first step towards microelimination. / Prevalencia de la infección por el VHC en un área sanitaria de Madrid: el primer paso para la microeliminación.

OBJECTIVE: To estimate the prevalence of HCV infection in the general population of a health area through an intervention in Primary Care, differentiating between new diagnoses and infections previously diagnosed but not treated. METHODS: Participants were selected through a risk assessment questionnaire, with all those who gave at least one affirmative answer and all those over 50 years of age undergoing a rapid test. Positive tests were confirmed in the lab by determination of anti-HCV antibodies by chemiluminescent microparticle immunoassay and determination of viraemia. RESULTS: Of the 7,991 participants, 36.2% presented a positive HCV risk questionnaire. 4,717 tests were performed, finding an anti-HCV percentage of 0.65% in the screened population, with 0.46% of active infections. Among the individuals with a positive test result, 51.9% had a known prior diagnosis but had not received treatment, because they were not aware of it or were not linked to the health system, and 19.2% had a positive result for the first time. The prevalence of hidden infection was higher in men, those over 50 years of age and people from Eastern Europe. CONCLUSION: We found a prevalence of active infections higher than recently described nationwide, and a higher percentage of newly diagnosed infections than recent similar studies in other areas. These differences justify the need to perform local assessments of the prevalence of HCV infection in each of the health areas where it is planned to implement and monitor a microelimination programme.

Outcome of an HIV education program for primary care providers: Screening and late diagnosis rates.

BACKGROUND: Late HIV diagnosis remains one of the challenges in combating the epidemic. Primary care providers play an important role in screening for HIV infection. Our study aims to evaluate the relationship between knowledge and barriers to HIV testing and screening outcomes. The impact of an education program for primary care providers, towards improving HIV testing and late diagnosis rates, is also assessed. METHODS: A self-administered questionnaire that was developed within the framework of the European project OptTEST was used to examine HIV knowledge and barriers to HIV testing scores before and after being involved in an HIV education program. A quasi-experimental design with pre- and post-intervention measures was performed to investigate its impact. We performed multivariable logistic regression analysis to assess the relationship between variables for the HIV testing offer. RESULTS: A total of 20 primary care centers and 454 primary care staff were included. Baseline OptTEST results showed that more knowledgeable staff offered an HIV test more frequently (OR 1.07; CI 95% 1.01-1.13; p = 0.027) and had lower barrier scores (OR 0.89; CI 95% 0.77-0.95; p = 0.005). Nurses had lower scores in knowledge-related items (OR 0.28; CI 95% 0.17-0.46; p<0.001), but higher scores in barrier-related items than physicians (OR 3.28; CI 95% 2.01-5.46; p<0.001). Specific centers with more knowledgeable staff members had a significant association with a greater level of new HIV diagnosis rates (OR 1.61; CI 95% 1.04-2.49; p = 0.032). After the intervention, we found that 12 out of 14 individual questions showed improved scores. In the 6 months after the training program, we similarly found a higher HIV testing rate (OR 1.19; CI 1.02-1.42; p = 0.036). CONCLUSIONS: This study highlights the association between knowledge and barriers to HIV testing, including HIV testing rates. It shows that it is possible to modify knowledge and reduce perceived barriers through educational programs, subsequently improving HIV screening outcomes.

A scoring system for prescribing fidaxomicin in Clostridium diffícile infection. / Uso de un sistema de puntuación para la prescripción de fidaxomicina en la infección por Clostridium difficile.

Recurrences of Clostridium difficile infections lead to hospital readmissions and high costs, in addition to the suffering and frustration for the patients. Fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection. Despite this superiority, its high cost has led to very restrictive policies in its use, as such that many institutions only use it in patients with multiple recurrences. While waiting for new predictive clinical tools, we propose the development of scoring systems that allow the more high-risk patients to be treated earlier.

Pre-exposure prophylaxis (PrEP) against HIV: efficacy, safety and uncertainties.

Despite the global stabilization of the number of new HIV infections in recent years, there has been an increase in new infections among men who have sex with men. This fact indicates the lack of effectiveness of the measures and prevention campaigns established so far for this group.  It is therefore necessary to implement alternative preventive measures for them. Pre-exposure pharmacological prophylaxis (PrEP) is one of the best evaluated options and has had high protection rates in both clinical and real-life trials. The strategy has also shown an adequate profile in terms of safety, tolerance, adverse effects and cost-effectiveness in the studies carried out to assess this important topic.

En los últimos años se ha objetivado un incremento de las nuevas infecciones por el VIH en el grupo de hombres que tienen sexo con hombres, lo que indica la ausencia de eficacia de las campañas y medidas preventivas instauradas en dicho grupo.Es necesario, por tanto, implementar medidas preventivas alternativas, siendo la profilaxis farmacológica pre-exposición (PrEP) una de las opciones mejor evaluadas tanto en ensayos clínicos como en la vida real, habiéndose demostrado tasas de protección superiores al 80% cuando se administra en los casos indicados y con buen cumplimiento terapeútico.La estrategia ha demostrado, además, un perfil adecuado en seguridad,tolerancia y efectos adversos, siendo además coste-efectiva según losestudios realizados para valorar este importante aspecto.

Uso de un sistema de puntuación para la prescripción de fidaxomicina en la infección por Clostridium difícil / A scoring system for prescribing fidaxomicin in Clostridium diffícile infection

Las recurrencias de la infección por Clostridium difficile ocasionan reingresos hospitalarios y costes elevados, además de sufrimiento y frustración para los pacientes que las padecen. Recientemente se ha incorporado fidaxomicina, un nuevo antibiótico con cuya utilización se ha demostrado una reducción significativa de las recurrencias de esta infección. A pesar de esta superioridad, su elevado coste ha ocasionado políticas muy restrictivas en su utilización hasta el punto de que en muchas instituciones solo se emplea para pacientes con múltiples episodios. En espera de herramientas clínicas predictivas, proponemos el desarrollo de sistemas de puntuación que permitan tratar más precozmente a pacientes de alto riesgo (AU)

Recurrences of Clostridium difficile infections lead to hospital readmissions and high costs, in addition to the suffering and frustration for the patients. Fidaxomicin has recently been introduced as a new antibiotic that has been shown to significantly reduce the recurrence of this infection. Despite this superiority, its high cost has led to very restrictive policies in its use, as such that many institutions only use it in patients with multiple recurrences. While waiting for new predictive clinical tools, we propose the development of scoring systems that allow the more high-risk patients to be treated earlier (AU)

Prevalencia de la infección por el VHC en un área sanitaria de Madrid: el primer paso para la microeliminación / Prevalence of HCV infection in a health area of Madrid (Spain): The first step towards microelimination

OBJETIVO: Estimar la prevalencia de la infección por VHC en la población general de un área sanitaria a través de una intervención en Atención Primaria, diferenciando entre nuevos diagnósticos e infecciones previamente diagnosticadas pero no tratadas. MÉTODOS: Se seleccionaron participantes mediante un cuestionario de evaluación de riesgo, realizando un test rápido a todos aquellos con alguna respuesta afirmativa y a todos los mayores de 50 años. Las pruebas positivas se confirmaron en el laboratorio mediante determinación de anticuerpos frente al VHC por enzimoinmunoensayo de micropartículas quimioluminiscente y determinación de la viremia. RESULTADOS: Del total de 7.991 participantes, el 36,2% presentó cuestionario de riesgo para VHC. Se realizaron 4.717 test, encontrando una proporción de anti-VHC de 0,65% en la población cribada, quedando en 0,46% de infecciones activas. El 51,9% de las personas con test positivo tenían un diagnóstico previo conocido pero no habían recibido tratamiento, por no ser conscientes de ello o no encontrarse vinculados al sistema sanitario, y el 19,2% tuvo un resultado positivo por primera vez. La prevalencia de infección oculta fue mayor en hombres, mayores de 50 años, y personas procedentes de Europa del Este. CONCLUSIÓN: Encontramos una prevalencia de infecciones activas superior a la descrita recientemente a nivel nacional, y con mayor porcentaje de pacientes nuevamente diagnosticados que en trabajos similares en otras áreas. Estas diferencias justifican la necesidad de realizar evaluaciones locales de la prevalencia de infección por VHC en cada una de las áreas de salud donde se plantee implementar y monitorizar un programa de microeliminación

OBJECTIVE: To estimate the prevalence of HCV infection in the general population of a health area through an intervention in Primary Care, differentiating between new diagnoses and infections previously diagnosed but not treated. METHODS: Participants were selected through a risk assessment questionnaire, with all those who gave at least one affirmative answer and all those over 50 years of age undergoing a rapid test. Positive tests were confirmed in the lab by determination of anti-HCV antibodies by chemiluminescent microparticle immunoassay and determination of viraemia. RESULTS: Of the 7,991 participants, 36.2% presented a positive HCV risk questionnaire. 4,717 tests were performed, finding an anti-HCV percentage of 0.65% in the screened population, with 0.46% of active infections. Among the individuals with a positive test result, 51.9% had a known prior diagnosis but had not received treatment, because they were not aware of it or were not linked to the health system, and 19.2% had a positive result for the first time. The prevalence of hidden infection was higher in men, those over 50 years of age and people from Eastern Europe. CONCLUSION: We found a prevalence of active infections higher than recently described nationwide, and a higher percentage of newly diagnosed infections than recent similar studies in other areas. These differences justify the need to perform local assessments of the prevalence of HCV infection in each of the health areas where it is planned to implement and monitor a microelimination programme

Intoxicación por "agua de cocción de chochos" / Lupin beans (chochos) poisoning

Se presenta un caso clínico poco habitual de intoxicación secundaria a ingesta de alcaloides procedentes de altramuces, consumidos con frecuencia por su valor nutricional. Se describen los efectos adversos más frecuentes tras la ingesta de lupino, que incluyen: síntomas anticolinérgicos y alteraciones del SNC leves y se expone el manejos de su intoxicación. El caso ilustra la dificultad que entraña el diagnóstico y la importancia de una buena anamnesis y exploración fisica detalladas (AU)

An unusual clinical case of secondary poisoning after intake of lupine alkaloids, often consumed for its nutritional value is presented. Most frequent side effects after intake of lupine are described, including anticholinergic symptoms and mild CNS disorders and management of poisoning is discussed. The case illustrates the difficulty of diagnosis and the importance of a good history and detailed phusical examination (AU)