Uso do Ganciclovir no tratamento da Covid-19 / Use of Ganciclovir in the treatment of Covid-19

Desde os primeiros surtos da doença provocada pelo novo coronavírus (SARS-CoV-2), que se disseminou rapidamente pelo mundo, há um interesse crescente em encontrar um potencial agente terapêutico para a doença. A prática atual para tratar COVID-19 é variável, o que reflete a incerteza em grande escala e, para tentar sanar essa incerteza, numerosos ensaios clínicos randomizados de diferentes medicamentos estão em andamento com o intuito de melhor orientar a clínica (WHO,2020). Até o momento os trabalhos acerca do uso do ganciclovir para tratar pacientes que contraíram a doença são escassos e ainda não foram realizados ensaios clínicos com este fármaco, apenas relatos e séries de caso foram localizados na literatura. Considerando os estudos analisados e a pirâmide de evidência proposta pelo Oxford Center for Evidence-Based Medicine (figura 02), ainda não existe evidência robusta para sustentar a utilização deste fármaco, em larga escala, no tratamento da COVID-19.

Since the first outbreaks of the disease caused by the new coronavirus (SARS-CoV-2), which has spread rapidly around the world, there is a growing interest in finding a potential therapeutic agent for the disease. The current practice to treat COVID-19 is variable, which reflects large-scale uncertainty and, to try to address this uncertainty, numerous randomized clinical trials of different drugs are underway in order to better guide the clinic (WHO,2020). To date, studies on the use of ganciclovir to treat patients who contracted the disease are scarce and no clinical trials have been conducted with this drug, only reports and case series have been found in the literature. Considering the studies analyzed and the pyramid of evidence proposed by the Oxford Center for Evidence-Based Medicine (figure 02), there is still no robust evidence to support the use of this drug, on a large scale, in the treatment of COVID-19.

Retinite por citomegalovírus em paciente com Síndrome de Good / Cytomegalovirus retinitis in Good Syndrome

Resumo A Síndrome de Good é uma síndrome paraneoplásica caracterizada pela associação de timoma e hipogamaglobulinemia, cursando com imunossupressão. Relatamos um caso raro de retinite por citomegalovírus em paciente com esta síndrome.

Abstract Good syndrome is a paraneoplastic syndrome characterized by the association of thymoma and hypogammaglobulinemia, with immunosuppression. We report a rare case of cytomegalovirus retinitis in a patient with this syndrome.

Desafíos terapéuticos en la enfermedad injerto contra huésped / Therapeutic challenges in graft versus host disease

La enfermedad injerto contra huésped es una entidad en la cual las células inmunológicas competentes de un tejido injertado reconocen y dañan antígenos presentes en el receptor del trasplante, que es incapaz de defenderse de ellas. Es una complicación frecuente del trasplante alogénico de médula ósea, y con menor frecuencia se produce luego de trasplantes de órganos sólidos o transfusiones de hemoderivados no irradiados. Se comunica el caso de una paciente de sexo femenino de 23 años, con leucemia linfoblástica aguda.y trasplante alogénico de médula ósea, que presentó una enfermedad injerto contra huésped con compromiso cutáneo y gastrointestinal dependiente de corticoides, con mejoría de los signos y síntomas cutáneos luego del tratamiento con infliximab y fotoféresis extracorpórea. (AU)

Graft versus host disease is an entity in which competent grafted immune cells recognize and damage tissue antigens present in the transplant recipient, who is unable to defend from them. It is one of the most serious complications in patients undergoing allogeneic bone marrow transplantation, although less frequently it may be associated with solid organ transplants or transfusions of not irradiated blood products. We report the case of a 23 year-old patient with acute lymphoblastic leukemia and allogeneic bone marrow transplantation, that presented graft versus host disease with skin and gastrointestinal involvement, dependent on corticosteroids, that showed improvement in signs and skin symptoms after treatment with infliximab and extracorporeal photopheresis. (AU)

Efectividad y seguridad de valganciclovir comparado con ganciclovir, valaciclovir y aciclovir, en pacientes receptores de trasplante de órganos sólidos / Effectiveness and safety of valganciclovir compared to ganciclovir, valaciclovir and acyclovir in patients receiving solid organ transplantation

Introducción: Valganciclovir es un medicamento de uso oral, que se metaboliza rápidamente a ganciclovir y es una opción para la profilaxis y el tratamiento de la infección por citomegalovirus en pacientes receptores e trasplante de órgano sólido. Esta evaluación tecnológica se desarrolló en el marco de la actualización integral del Plan Obligatorio de Salud para el año 2015. Objetivo: Evaluar la efectividad y seguridad del uso de valganciclovir para la prevención y el tratamiento de infección por citomegalovirus comparada con gancinclovir, valaciclovir y aciclovir en pacientes receptores de trasplante de órgano sólido. Metodología: La evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS, con restricción al idioma inglés y español y limitada a revisiones sistemáticas publicadas en los últimos cinco años y ensayos clínicos sin restricción de tiempo. Las búsquedas electrónicas fueron hechas entre octubre y diciembre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por un revisor. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad. La calidad de los estudios fue valorada con la herramienta de riesgo de sesgo de la Colaboración Cochrane. Las características de los estudios fueron extraídas a partir de las publicaciones originales. Se realizó una síntesis narrativa de las estimaciones del efecto para las comparaciones y desenlaces de interés a partir de los estudios de mejor calidad. Se estimaron medidas combinadas del efecto a través de un metanálisis con el método de Mantel-Haenszel y un modelo de efectos aleatorios, empleando el programa RevMan 5.2. Resultados: En relación a efectividad: Valganciclovir es tan efectivo como ganciclovir intravenoso y valaciclovir oral en la profilaxis de enfermedad por citomegalovirus en pacientes receptores de trasplante de órgano sólido, pues no se encontraron diferencias con significancia estadística en los desenlaces enfermedad por citomegalovirus a los seis y doce meses (RR=0.76 (0.47, 1.24) y RR 0.93 (0.60, 1.44) respectivamente), rechazo del órgano trasplantado a los seis y doce meses (RR 0.85 (0.64, 1.14) y RR 0.78 (0.49, 1.23)) y supervivencia del paciente al año (RR=1.01 (0.97, 1.06). Valganciclovir es tan efectivo como ganciclovir oral en el tratamiento de enfermedad por CMV de pacientes receptores de trasplante de órgano sólido, pues no se encontraron diferencias con significancia estadística en los desenlaces cura clínica a los 21 días (77.4% para valganciclovir oral y 80.3% ganciclovir intravenoso, p=no significativa), cura clínica a los 49 días (85.4% para valganciclovir oral y 84.1% ganciclovir intravenoso, p=no significativa) y supervivencia del paciente a los 49 días. En relación a seguridad: Valganciclovir es tan seguro como ganciclovir y valaciclovir en la producción de eventos adversos, sin embargo, tiene una menor proporción de eventos adversos que lleven a la suspensión del medicamento antiviral (RR=0.1, (0.02, 0.51)), en el escenario de la profilaxis universal de la infección por CMV en pacientes receptores de trasplante de órgano sólido. Conclusiones: Valganciclovir es similar en seguridad y eficacia que ganciclovir intravenoso y valaciclovir oral en el escenario de la profilaxis de la infección por CMV en el paciente receptor de trasplante de órgano sólido y además valganciclovir es semejante a ganciclovir intravenoso en el tratamiento de esta infección en esta misma población.(AU)

A Case of CMV Endotheliitis Treated with Intravitreal Ganciclovir Injection

We report a case of CMV corneal endotheliitis that was treated with intravitreal ganciclovir injection. A 56-year-old man who has suffered from uveitis was referred to our clinic due to corneal endothelial abnormality. Slit lamp examination showed a localized sectoral corneal edema and linear keratic precipitates along the boundary of edema. In spite of treatment with oral steroid and acyclovir, the disease progressed and two new coin-like lesions were developed. After topical ganciclovir and intavitreal injection of ganciclovir, the corneal lesions disappeared.

A Case of CMV Endotheliitis Treated with Intravitreal Ganciclovir Injection

We report a case of CMV corneal endotheliitis that was treated with intravitreal ganciclovir injection. A 56-year-old man who has suffered from uveitis was referred to our clinic due to corneal endothelial abnormality. Slit lamp examination showed a localized sectoral corneal edema and linear keratic precipitates along the boundary of edema. In spite of treatment with oral steroid and acyclovir, the disease progressed and two new coin-like lesions were developed. After topical ganciclovir and intavitreal injection of ganciclovir, the corneal lesions disappeared.

Uso de ganciclovir 0,15 por cento gel para tratamento de ceratoconjuntivite adenoviral / Ganciclovir 0.15 percent ophthalmic gel in the treatment of adenovirus keratoconjuntivitis

OBJETIVOS: Determinar a efetividade e a toxicidade do ganciclovir 0,15 por cento gel no tratamento de ceratoconjuntivites adenovirais e na prevenção de complicações tais como infiltrados corneanos, membranas ou pseudomembranas conjuntivais. MÉTODOS: Ensaio clínico duplo-cego, intervencionista, randomizado. Os 33 pacientes com diagnóstico clínico de ceratoconjuntivite adenoviral com início dos sintomas há menos de cinco dias foram randomizados em dois grupos: Grupo 1 (tratamento) com 19 pacientes que usaram ganciclovir e Grupo 2 (controle) com 14 pacientes que usaram lágrima artificial sem conservante. Todos pacientes responderam a um questionário de sinais e sintomas e foram submetidos a um exame oftalmológico. No 6º dia de tratamento responderam ao mesmo questionário por telefone e no 10º dia foram reavaliados pelo mesmo examinador e responderam novamente ao questionário. Os sinais e sintomas foram comparados. Para análise estatística foi utilizado os testes T de Student, Mann-Whitney e Wilcoxon, com significância estatística p<0,05. RESULTADOS: Tendência de melhor resposta no grupo tratamento em relação à percepção pelos pacientes, além da melhora mais rápida desse grupo em relação ao grupo controle (p=0,26). Houve menor transmissão para o olho adelfo (p=0,86) e para pessoas do convívio (p=0,16) no grupo tratamento. Comparando os dois grupos não houve diferença estatística em relação aos sintomas e sinais da conjuntivite. Comparando isoladamente cada grupo entre o pré-tratamento e no decorrer do tratamento, observou-se melhora estatisticamente significativa da dor, prurido e fotofobia apenas no grupo tratamento. Ganciclovir não mostrou toxicidade e teve maior tolerância pelos pacientes. Não houve diferença significativa no aparecimento de complicações da conjuntivite entre os dois grupos. CONCLUSÕES: O estudo evidenciou uma tendência à melhora mais rápida dos sinais e sintomas dos pacientes tratados com ganciclovir em relação ao grupo ...

PURPOSE: To evaluate the efficacy and the toxicity of 0.15 percent ganciclovir gel in the treatment of adenoviral conjunctivitis and in preventing ocular complications after adenoviral conjunctivitis, such as corneal infiltrates and pseudomembranes. METHODS: Double blind, interventional and randomized clinical trial. Thirty-three patients with clinical diagnosis of adenoviral conjunctivitis with onset of symptoms for five or less days were randomized in two groups: Group 1 (treatment) with 19 patients used ganciclovir gel and Group 2 (control) with 14 patients used artificial tears without preservative. Patients answered a questionnaire of signs and symptoms and were submitted to an ophthalmologic exam. On the 6th and 10th days of treatment they answered the same questions and were re-examined by the same ophthalmologist. Signs and symptoms were compared. T Student, Mann-Whitney e Wilcoxon tests were used to statistical analysis. RESULTS: Trend of better response in the treatment group in relation of patients' perception, besides faster improvement of this group compared to the control group (p=0.26). There were lower transmission to the fellow eye (p=0.86) and to people living together (p=0.16) in the treatment group. No statistical difference related to signs and symptoms of conjunctivitis were found comparing both groups. We observed statistical difference in pain, itch and photophobia only in the treatment group, comparing each group alone. No toxicity and more tolerance of the ganciclovir were observed. There was no statistical difference in the ocular complications after conjunctivitis between both groups. CONCLUSIONS: This study showed trend of better and faster response of the signs and symptoms of the patients treated with ganciclovir compared with the control group, but with no statistical significant. These results need to be confirmed by additional studies, with more patients and longer follow-up. Clinical Trails.gov: NCT01349452.

Treatment of cytomegalovirus (CMV) retinitis with intravitreous ganciclovir in HIV-infected children.

OBJECTIVES: To evaluate the efficacy, visual outcomes, and complications of intravitreous ganciclovir treatment in cytomegalovirus (CMV) retinitis in HIV-infected children. MATERIAL AND METHOD: The medical records of HIV-infected children who were screened for CMV retinitis from February 2002 to February 2005 were reviewed. The children with CD4+ < 15%, or with clinical category C would have complete ophthalmic examination every 3 months. Ganciclovir (4 mg/0.04 ml) was administered intravitreously to the eye with CMV retinitis every 2 weeks under general anaesthesia. After injection, fundi were examined immediately, 1 day, 14 days and every 2 weeks until the lesions were stable. RESULTS: Six (9 eyes) out of 45 children (13%) aged 2-12 years were found to have CMV retinitis. All CMV retinitis lesions were "cheese and ketchup like" (retinal hemorrhage and exudate) lesions and presented in the posterior pole. Bilateral CMV retinitis were found in 3 children. Intravitreous ganciclovir was injected in 4 children (5 eyes). The average number of intravitreous injections for each patient was 5.6 (3-7) times. All of the children received antiretroviral therapy and 3 children also received intravenous ganciclovir CMV retinitis lesions were improved in every eye. The visual acuity (VA) remained stable in 4 eyes, but endophthalmitis developed in one eye a few days after injection. The average duration of follow-up was 13.5 months (3-23 months). CONCLUSION: CMV retinitis was not uncommon. The authors found that intravitreous ganciclovir was effective but may cause complications. This treatment should be considered in a resource-limited setting.

The incidence of cytomegalovirus infection in lung transplant recipients under universal prophylaxis with intravenous ganciclovir

The best strategy for control of cytomegalovirus (CMV) infection in lung transplant patients is still not determined. The aim of this study was to document the incidence of CMV infection in a cohort of lung transplant recipients under universal prophylaxis with intravenous ganciclovir. All patients received immunosuppressive regimens consisting of cyclosporine, azathioprine, and prednisone. Regardless of CMV serostatus, intravenous ganciclovir was prescribed for every patient in the first 3 months post-transplantation. CMV infection was defined as the detection of CMV pp65 in leukocytes. Eighty-two lung transplant patients were included over a 5-year period. The incidence of CMV infection in the first year post-transplantation was 68.3 percent, occurring after a median length of 114 days (range, 26-343 days). This study revealed a high incidence of CMV infection in the first year following lung transplantation despite prolonged universal ganciclovir prophylaxis.

The high-dose, alternate-week intravitreal ganciclovir injections for cytomegalovirus retinitis in acquired immune deficiency syndrome patients on highly active antiretroviral therapy.

OBJECTIVES: To evaluate the efficacy, and complications of the high-dose, alternate-week, intravitreal ganciclovir injection for cytomegaloviral retinitis (CMVR) in acquired immune deficiency syndrome (AIDS) patients on highly active antiretroviral therapy (HAART). DESIGN: Retrospective case series. PARTICIPANTS: AIDS patients with CMVR and on HAART MATERIAL AND METHOD: The high-dose, 4 mg/0.1 ml, ganciclovir was injected intravitreally to the enrolled patients on an alternate-week basis. The patients were monitored clinically until the retinitis was inactive, then the injections were withdrawn. The injections were re-initiated if relapse occurred. MAIN OUTCOME MEASURES: The number of eyes achieved inactive retinitis and corresponded to the number of injections, number of relapses and corresponded duration, visual acuity during the injection, and complications of the injection. RESULTS: Inactive lesions were found in 42/51 eyes (82.40%), the corresponding mean number of injections was 5.4 (1-18) per eye. There was no relapse and the corresponded duration of follow-up was 5.1 months (1-16). The final visual outcomes were improved or stable in 26 eyes (50.9%). These visual outcomes were statistically related to initial visual acuity (p = 0.022) but not statistically related to the number of injections (p = 0.929). Complications were found in 7/51 eyes (13.7%). They were vitreous haze, immune recovery uveitis, rhegmatogenous retinal detachment, and infectious endophthalmitis. CONCLUSION: The high-dose, alternate-week, intravitreal injection of ganciclovir may be an alternative for the treatment of CMVR in AIDS patients who are on HAART However, the induction course is longer than the weekly regimen and close monitoring of patients is essential.

Treatment of cytomegalovirus retinitis in AIDS patients with intravitreal ganciclovir.

BACKGROUND: Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection in AIDS patients, and frequently leads to blindness if untreated. Intravitreal ganciclovir proved to be effective in stopping the progression of the disease. OBJECTIVES: To determine the efficacy and complications of intravitreal ganciclovir (2 mg in 0.1 ml per injection) to control CMV retinitis. STUDY DESIGN: A retrospective non-randomized interventional case series. MATERIAL AND METHOD: The participants were 363 consecutive patients with CMV retinitis treated at the CMV Retinitis Clinic, Maharaj Nakorn Chiang Mai Hospital over the period from June 2001 to December 2003. The affected eyes received weekly intravitreal injections of 2 mg of ganciclovir until the lesions were inactive, then 2-4 weeks each time continuously or until relapse. If the lesions relapsed, then the weekly schedule was re-started. RESULTS: In 568 treated eyes at the time of last follow up, visual acuity remained stable in 343 (60%), improved in 76 (13%), and decreased in 149 (26%). Of these, 33 retinal detachments, 6 intravitreal hemorrhages, 6 endophthalmitis, and 2 cataract occurred. Bilateral disease occurred in 22% of patients who first came with unilateral involvement. CONCLUSION: Intravitreal ganciclovir appeared to be a worthwhile therapeutic alternative for CMV retinitis patients with unaffordable or intolerant to systemic anti-CMV therapy, but the complications of intravitreal injections should also be recognized.

Treatment of cytomegalovirus retinitis in acquired immunodeficiency syndrome with intravitreal ganciclovir implant.

To determine the efficacy and complication of the sustained-release intravitreal ganciclovir implanted to control cytomegalovirus (CMV) retinitis in acquired immunodeficiency syndrome (AIDS) patients, a prospective study with intravitreal ganciclovir devices placed in 5 eyes was conducted. No concomitant systemic anti-CMV therapy was used. The results showed that retinitis was controlled in all cases. Visual acuity improved dramatically within three weeks postoperatively and maintained for a mean period of 5.6 months. The best corrected postoperative visual acuity of the groups was not statistically significantly different from the preoperative measurement, (P=0.06, one-tailed test). Serious ocular complications were not encountered. As such the implant offers a promising alternative for local control of CMV retinitis associated with AIDS. The vision was improved and stabilized with functional vision.

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant

The objective of this prospective study was to evaluate the efficacy and complications of the use of an intraocular sustained-release ganciclovir implant for the treatment of active cytomegalovirus (CMV) retinitis in AIDS patients. Thirty-nine eyes of 26 patients were submitted to ocular surgery. All patients underwent complete ocular examination before and after surgery. The surgical procedure was always done under local anesthesia using the same technique. The mean time for the surgical procedure was 20 min (range, 15 to 30 min). The average follow-up period was 3.7 months. Of all patient, only 4 presented recurrence of retinitis after 8, 8, 9 and 2 months, respectively. Three of them received a successful second implant. All 39 eyes of the 26 patients presented healing of retinitis as shown by clinical improvement evaluated by indirect binocular ophthalmoscopy and retinography. Retinitis healed within a period of 4 to 6 weeks in all patients, with clinical regression signs from the third week on. Six (15.4 percent) eyes developed retinal detachment. None of the patients developed CMV retinitis in the contralateral eye. The intraocular implant proved to be effective in controlling the progression of retinitis for a period of up to 8 months even in patients for whom systemic therapy with either ganciclovir or foscarnet or both had failed. The intraocular sustained-release ganciclovir implant proved to be a safe new procedure for the treatment of CMV retinitis, avoiding the systemic side effects caused by the intravenous medications and improving the quality of life of the patients.

Infección por virus de la inmunodeficiencia humana: actualidades en el tratamiento / H.I.V. infections: Current treatment concepts

Ante el aumento progresivo de nuevos casos del síndrome de inmunodeficiencia adquirida (SIDA) en México, presentamos esta revisión de los medicamentos y sustancias que actualmente se encuentran en diversas fases de investigación clínica para el tratamiento de esta infección que, sin duda, es la pandemia más importante de la segunda mitad del siglo veinte. También revisamos las indicaciones en los pacientes con SIDA. Asimismo, se incluyen los medicamentos adyuvantes en el tratamiento de las complicaciones de la infección, su uso y efectos adversos, así como sus interacciones medicamentosas

Cytomegalovirus retinitis in AIDS patients: a clinical review

Cytomegalovirus (CMV) retinitis is an ocular condition previously seen in organ transplant recipients, patient on chemotherapy for malignancy, and in infants with congenital infections. As it present in immunocompromised, the AIDS patient has integrated this group of patients that can present with CMV retinitis. Moreover, it is the leading cause of opportunistic ocular infection in the AIDS patient, and the second most common ocular manifestation. As new drugs and modes of administration are studied that can effectively halt this progressively blinding condition, the awareness and recognition of CMV retinitis on AIDS patients has become increasingly important. This author will review the epidemiology, clinical presentation, and differential diagnosis of this condition. The current treatments being used and complications will also be discussed

Infección letal por citomegalovirus / Lethal infection by cytomegalovirus

Se describe un niño previamente sano e inmunocompetente,que desarrolla una infección generalizada por citomegalovirus,a la edad de 12 meses.El paciente había sido tratado en otra institución por neumonía con derrame y convulsiones febriles.Fue derivado a nuesta unidad de Terapia Intensiva ante la inminecia de fallo respiratorio.Todos los cultivos bacteriológicos y las pruebas de látex fueron negativas.La detección del antígeno precoz para CMV permitió confirmar el diagnóstico sugerido por la imágen radiológica.Los estudios unmunológicos no permitieron detectar alteraciones de la respuesta inmune.El tratamiento con ganciclovir no evitó el deterioro del paciente quien falleció al sexto día de hospitalización.La autopsia confirmó el diagnóstico de infección multisitémica con CMV.Se presenta una revisión de la bibliografía ï

Tratamiento con ganciclovir en neumonía intersticial por citomegalovirus / Treatment with ganciclovir of cytomegalovirus insterstitial pneumonia

La neumonía es una de las manifestaciones más frecuentes de infección por citomegalovirus en pacientes inmunosuprimidos, con letalidad cercana a 100% hasta el uso de ganciclovir. Se describe el caso de un preescolar con linfoma no Hodgkin que ingresó a una unidad de tratamiento intensivo a causa de choque séptico a Haemophilus influenzae, serotipo b, no productor de ß lactamasa, secundario a aplasia medular por quimioterapia. Evolucionó con neumonía intersticial, que obligó a mantenerlo conectado a un ventilador mecánico, con resultados negativos en los cultivos bacteriológicos para aerobios, anaerobios y hongos, por lo que se usaron infructuosamente diversos esquemas antibióticos como prueba terapéutica. Como no mejoró su función respiratoria, se realizó biopsia pulmonar a cielo abierto, encontrándose alteraciones sugerentes de neumonía intersticial por citomegalocirus. Los cultivos para el virus fueron negativos, pero la inmunofluorescencia IgG mostró un título de 1:128, si bien la de IgM era negativa. Se hizo tratamiento con ganciclovir sódico 10 mg por kg por día, en coincidencia con lo cual el paciente inició un curso favorable, siendo posible desconectarle del ventilador mecánico algunos días más tarde. Dos meses después había mejorado clínica y radiológicamente. No se registraron efectos adversos renales, hepáticos y hematológicos del tratamiento