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Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV- patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status.

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Introducción: El síndrome de Evans es un desorden autoinmune poco frecuente, caracterizado por el descenso de al menos dos líneas celulares hemáticas. Las publicaciones del síndrome de Evans e infección por citomegalovirus resultan escasas. Objetivo: Examinar el caso de una niña con síndrome de Evans e infección activa por citomegalovirus que respondió favorablemente a la terapia antiviral. Presentación del caso: Niña de 13 meses con antecedentes de prematuridad y bajo peso al nacer, que acudió a consulta por presentar palidez y equimosis en tórax, abdomen y extremidades. En los exámenes de laboratorio se encontró trombocitopenia y anemia severa con prueba de Coombs directo positiva. Recibió pulsos de metilprednisolona con respuesta desfavorable. La carga viral resultó positiva para citomegalovirus (4019 copias de ADN) y recibió valganciclovir con evolución favorable en el seguimiento. Conclusiones: El síndrome de Evans asociado a infección por CMV es infrecuente. El tratamiento con valganciclovir podría ser beneficioso para cierto grupo de pacientes; sin embargo, hacen falta más estudios que demuestren la eficacia y seguridad de este tratamiento en este síndrome; más aún si está asociado a una elevada carga viral(AU)

Introduction: Evans syndrome is a rare autoimmune disorder, characterized by the descent of at least two blood cell lines. Publications of Evans syndrome and cytomegalovirus infection are scarce. Objective: To examine the case of a girl with Evans syndrome and active cytomegalovirus infection who responded favorably to antiviral therapy. Case presentation: A 13-month-old girl with a history of prematurity and low birth weight, who attended the consultation for presenting pallor and ecchymosis in the thorax, abdomen and extremities. Laboratory tests found thrombocytopenia and severe anemia after a positive direct Coombs test. She received pulses of methylprednisolone with unfavorable response. The viral load was positive for cytomegalovirus (4019 copies of DNA) and received valganciclovir with favorable evolution at follow-up. Conclusions: Evans syndrome associated with CMV infection is uncommon. Treatment with valganciclovir may be beneficial for a certain group of patients. However, more studies are needed to demonstrate the efficacy and safety of this treatment in this syndrome; even more so if it is associated with a high viral load(AU)

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From 2009-2015 to 2016-2019, the proportion of infants in the US with congenital cytomegalovirus treated with valganciclovir roughly doubled for infants enrolled with employer-sponsored insurance (from 16% to 29%) and Medicaid (from 16% to 36%). The proportion treated with valganciclovir increased for all congenital cytomegalovirus disease severity groups.

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Human herpesvirus-8 infection (HHV-8) is the causative agent of Kaposi sarcoma (KS) and is highly prevalent among people living with HIV (KS/HIV). It has been reported that valganciclovir (VGC) reduces HHV-8 replication in KS/HIV patients. However, currently it is unclear if VGC modifies the frequency and induces changes in markers of immune regulation of immune cells necessary to eliminate HHV8-infected cells, such as Natural Killer (NK) and NK T cells (NKT). This study evaluated the effect of VGC used as antiviral HHV8 therapy in KS patients on the frequency of NK and NKT subpopulations based on the CD27 and CD57 expression, and the immunosenescence markers, PD-1 and KLRG1. Twenty KS/HIV patients were followed-up at baseline (W0), 4 (W4), and 12 weeks (W12) of the study protocol. Among them, 10 patients received a conventional treatment scheme (CT), solely antiretroviral therapy (ART), and 10 patients received a modified treatment regime (MT), including VGC plus ART. In both groups, bleomycin/vincristine was administrated according to the treating physician's decision. The soluble levels of IL-15, PD-L1, PD-L2, and E-cadherin were quantified across the follow-up. Our results showed that the higher IL-15 levels and lower NK frequencies cells in KS/HIV patients reach almost normal values with both treatments regimes at W12. CD27+ NK and NKT cell frequencies increased since W4 on KS/HIV patients with MT. Furthermore, PD-1 expression decreased while KLRG1 increased on NK and NKT subpopulations at W12, and it is accompanied by increased PD-L1 plasma level since W4. Our study highlights the disruption of NK and NKT subpopulations in patients with KS/HIV and explores VGC treatment's contribution to immune reconstitution during the first weeks of treatment.

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Two simple, selective and sensitive spectrophotometric methods were developed and validated for the determination of valganciclovir hydrochloride (VLGH) in pure drug and tablets. The first method was based on the reduction of iron(III) to iron(II) by VLGH and subsequent formation of iron(III)-ferricyanide complex (Prussian blue) in acid medium which was measured at 730 nm (method A). In the second method (method B), permanganate was reduced by VLGH to bluish green manganate in alkaline medium and the absorbance was measured at 610 nm. The absorbance measured in each case was related to VLGH concentration. The experimental conditions were carefully studied and optimized. Beer's law was obeyed over the concentration ranges of 2.5-20.0 and 2.0-40.0 µg mL-1 for method A and method B, respectively, with corresponding molar absorptivity values of 1.28×104 and 6.88×103 L mol-1 cm-1. The limits of detection (LOD) and quantification (LOQ) were 0.11 and 0.33 µg mL-1 (method A) and 0.21 and 0.64 µg mL-1 (method B). Within-day and between-day relative standard deviations (%RSD) at three different concentrations levels were < 2.4%, and the respective relative errors (%RE) were ≤ 3%. The proposed methods were successfully applied to the determination of VLGH in tablets, and the results confirmed that the proposed methods were equally precise and accurate as the official method.

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Resumen Introducción: la infección viral más importante postrasplante renal es la infección por citomegalovirus (CMV), hay discrepancia entre centros y países en datos de incidencia de infección-enfermedad en esta población de pacientes. Diseño: se realiza un estudio observacional analítico, tomando una cohorte retrospectiva de pacientes mayores de 18 años, trasplantados renales de donante vivo o cadavérico entre el 2004 y 2015 con al menos seis meses de seguimiento. Material y métodos: se realiza muestreo no probabilístico por conveniencia, se toman los datos de las historias clínicas de los pacientes trasplantados renales, calculando la densidad de incidencia de infección-enfermedad por CMV y se describen las características clínicas y demográficas de los pacientes que presentaron estas patologías. Resultados: se analizaron 252 pacientes, encontrando 92.4% receptores con riesgo intermedio para CMV y 7.5% con riesgo alto, ninguno fue de riesgo bajo. Se identificaron 19 casos, 13 con infección (5.1%) y seis con enfermedad (2.3%). El compromiso gastrointestinal fue el más frecuente. El tiempo promedio desde el momento del trasplante hasta la aparición de la infección-enfermedad fue de 417 (±479) y 650 días (±481), respectivamente. La tasa de infección fue de 10.08 casos por 1000 pacientes/año y la tasa de enfermedad de 5.88 por 1000 pacientes/año. Conclusiones: la densidad de incidencia de infección-enfermedad por CMV en pacientes trasplantados renales fue de 10.08 casos y 5.88 casos por 1000 pacientes/año, respectivamente. Estas tasas son menores a las reportados en la literatura. Dada la baja frecuencia de eventos, no fue posible establecer factores de asociación.

Abstract Introduction: the most important viral infection after renal transplantation is cytomegalovirus (CMV) infection. There is a discrepancy between centers and countries in terms of incidence data of infection-disease in this population of patients. Design: an analytical observational study was conducted, taking a retrospective cohort of patients older than 18 years old, kidney transplant recipients of living or cadaveric donors between 2004 and 2015, with at least 6 months of follow-up. Material and methods: non-probability convenience sampling was done; data from the clinical records of the kidney transplant patients were taken, calculating the incidence density of CMV infection-disease and the clinical and demographic characteristics of the patients who presented these pathologies were described. Results: 252 patients were analyzed; 92.4% of recipients with intermediate risk for CMV and 7.5% with high risk were found. None of them had low risk. 19 cases were identified, 13 with infection (5.1%) and 6 with disease (2.3%). Gastrointestinal involvement was the most frequent. The average time from the time of transplant to the onset of the infection-disease was 417 (± 479) and 650 days (± 481), respectively. The infection rate was 10.08 cases per 1000 patients / year and the disease rate was 5.88 per 1000 patients/year. Conclusions: the incidence density of CMV infection-disease in renal transplant patients was 10.08 cases and 5.88 cases per 1000 patients / year, respectively. These rates are lower than those reported in the literature. Given the low frequency of events, it was not possible to establish association factors. (Acta Med Colomb 2018; 43: 20-23).

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This multicenter, open-label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty-six patients aged 4 months to 16 years received once-daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21.4%). There were fewer AEs during days 101-228 vs days 1-100. Twenty-seven patients (48.2%) had treatment-related AEs during valganciclovir treatment, most commonly leukopenia (21.4%), neutropenia (19.6%), anemia (7.1%), and tremor (5.4%). Treatment-related serious AEs were reported for nine patients (16.1%) and six withdrew due to AEs. Viremia was centrally confirmed in 10 patients; there was no confirmed CMV disease. One patient tested positive for a resistance mutation (UL97 L595F). Biopsy-proven acute rejection occurred in six patients (10.7%), but no graft loss or deaths occurred. In conclusion, up to 200 days of valganciclovir prophylaxis in pediatric kidney allograft recipients showed a safety profile consistent with that established in adult transplant patients.

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Objetivo: O estudo teve o objetivo de avaliar o panorama dos transplantes de órgãos sólidos (TOS) no Brasil e compreender as diferenças entre a profilaxia oral com valganciclovir e o tratamento preemptivo intravenoso com ganciclovir em pacientes de alto risco para desenvolvimento da doença pelo citomegalovírus (CMV) (D+/R-), e seu potencial impacto na desospitalização. Métodos: Por meio do Sistema de Informações Hospitalares do SUS (SIH/SUS), uma análise retrospectiva foi realizada para avaliar os principais centros de transplantes brasileiros e obter os TOS realizados em 2014. Os cálculos foram baseados na permanência hospitalar média por TOS, tempo de internação para cada abordagem farmacológica e número de pacientes D+/R-. A permanência hospitalar para tratamento preemptivo e profilaxia foram baseadas em diretrizes de uma instituição brasileira de referência. A taxa de infecção de CMV foi obtida de uma revisão da literatura. O desenvolvimento da doença pelo CMV após tratamento preemptivo ou profilaxia não foi considerado. Resultados:Em 2014, os centros de transplante avaliados realizaram um total de 6.912 TOS. O valganciclovir profilático proporcionou anualmente 21 dias a menos de hospitalização por paciente. A partir da relação do valor incremental (21 dias) entre a utilização de ganciclovir e valganciclovir e a média geral de permanência hospitalar no SUS para qualquer procedimento (5,6 dias), sugere-se que 3,75 novas internações por qualquer causa poderiam ocorrer por cada paciente em profilaxia. Conclusão: O valganciclovir profilático para pacientes D+/R- submetidos a TOS é potencialmente capaz de promover a desospitalização, permitindo maior comodidade ao paciente transplantado e utilização racional de recursos pela instituição

Objective: The study aimed to assess the landscape of solid organ transplants (SOT) in Brazil and understand differences between oral prophylaxis with valganciclovir and intravenous preemptive treatment with ganciclovir in patients at high risk for developing disease by cytomegalovirus (D+/R-), and their potential impact on deinstitutionalization. Methods: Based on the Brazilian Hospital Information System (SIH/SUS) database, a retrospective analysis was performed to assess the main Brazilian transplantation centers and obtain the SOT performed in 2014. The analysis was based on time of hospitalization according to SOT, LOS (Length of Stay) of each pharmacological approach and number of D+/R- patients. LOS for preemptive treatment and prophylaxis was taken from a Brazilian reference institution guideline. The CMV infection rate was obtained from a literature review. Development of CMV disease after both prophylaxis and preemptive treatment was not considered in the analysis. Results: In 2014, the transplant centers performed a total of 6,912 SOT. The valganciclovir prophylaxis resulted in reduction of 21 days of LOS per patient. Based on the ratio of incremental daily between the use of ganciclovir and valganciclovir (21 days) and overall mean hospital stay in the SUS to any procedure (5.6 days), it may be suggested that 3.75 new admissions for any cause could occur in addition, for each patient treated with prophylactic valganciclovir. Conclusion: Valganciclovir prophylaxis for patients D+ /R- undergoing TOS ispotentially able to promote deinstitutionalization, allowing greater convenience to patients transplanted and promoting the rational use of resources by the institution.

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Se presenta el caso de un lactante de 24 meses de edad diagnosticado de púrpura trombopénica corticodependiente, en el que se confirmó infección activa por citomegalovirus mediante serología y aislamiento del virus en orina. Ante la mala evolución de la enfermedad y sospechando relación causal con el virus, se inició valganciclovir vía oral hasta un total de 5 meses, obteniendo excelente respuesta con resolución simultánea de ambos procesos y sin efectos secundarios reseñables.

We report a case of a 24 months old child, diagnosed with corticodependent thrombocytopenia in which active cytomegalovirus infection was confirmed sustituir resaltado por: by means of serology and viris isolation in urine.. Due to the patient's worsening, we suspected a link between both processes and started oral valganciclovir, given for a total of 5 months. We documented excellent simultaneous response in both pathologies, and without relevant side effects.

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La infección congénita por citomegalovirus (CMV) es la principal etiología de hipoacusia neurosensorial de causa no genética. El uso de valganciclovir, un profármaco del ganciclovir con buena biodisponibilidad oral, es utilizado a nivel internacional como parte del tratamiento farmacológico. La indicación de tratamiento incluye a los recién nacidos sintomáticos con compromiso neurológico o con enfermedad órgano focal severa, dentro de los primeros 30 días de vida. El mayor beneficio del tratamiento en neonatos es la reducción del deterioro de la audición evitando la peoría de los umbrales auditivos, así como la mejoría en el neurodesarrollo. Un tratamiento inicial con ganciclovir, seguido de valganciclovir vía oral, ha demostrado mejor desempeño del desarrollo auditivo que el uso de terapia a corto plazo. Se reportan dos casos de citomegalovirus congénito, de diferente presentación clínica, en el período setiembre-octubre 2013. Se reporta mejoría sintomática tras el tratamiento con ganciclovir-valganciclovir en ambos casos. En el seguimiento con carga viral en orina, se observó una disminución mantenida de la misma durante el tratamiento. El principal efecto adverso fue la apariciónde anemia

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