Comparação de dois diferentes níveis de carga viral para início de tratamento antiviral na redução de riscos associados ao citomegalovírus em pacientes transplantados de rim sob estratégia preemptiva
Data
2024-07-24
Autores
Rocha, Ana Kleyce Correia 
Orientadores
Moura, Lúcio Roberto Requião
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
OBJETIVO: Demonstrar que o TP iniciado a partir de uma carga viral ≥ 2.500 UI/ml não aumenta os desfechos relacionados ao CMV em receptores de transplante de rim, quando comparado com o tratamento de qualquer viremia positiva, mas reduz eventos adversos relacionados à exposição ao antiviral. MÉTODOS: estudo de coorte retrospectiva que incluiu receptores de transplante de rim de doador falecido transplantados entre julho de 2012 a fevereiro de 2020 no programa de transplante de rim da SBIBAE. Em 1 de dezembro de 2015 a equipe assistencial modificou o limite de carga viral de CMV (RT-PCR) para início do TP de > 180 UI/ml (era 1) para ≥ 2.500 UI/ml (era 2), desenhando assim um experimento natural. O tempo de acompanhamento foi de até um ano após o transplante. O desfecho primário foi a leucopenia grave com necessidade de filgrastim durante o tratamento antiviral e os desfechos secundários de eficiência foram doença ou doença invasiva pelo CMV e de segurança a recidiva. Variáveis numéricas foram comparadas por teste U de ann-Whitney e variáveis categóricas e desfechos binários por teste X2. Adicionalmente, a cinética da carga viral durante o tratamento foi avaliada por estimativas de equações generalizadas, com ajuste por teste de Bonferroni. RESULTADOS: Dos 347 pacientes transplantados no período, 158 foram incluídos no estudo. Eles tinham 51,9 anos, 57,6% eram homens, 58,9% brancos e realizaram transplante após 4,1 anos em diálise. Os doadores tinham 45,0 anos, 19,6% eram de critério expandido, a perfusão foi híbrida em 86,1% e o tempo de isquemia fria foi de 33 horas. A dose acumulada de timoglobulina foi de 325 mg, distribuídas em 4 doses; 56,3% tiveram atraso na função do enxerto. Utilizando o critério de cada era, apenas 13 pacientes (8,2%) não fizeram tratamento para o CMV: 21,5% tiveram doença, 3,5% doença invasiva e o restante era assintomático. O tratamento foi realizado com Ganciclovir em 32,7% e Valganciclovir em 67,6%. Do total de pacientes, 34 eram da era 1 e 124 da era 2, não havendo diferenças na demografia de receptores e doadores de acordo com as eras. As frequências de primeira infecção pelo CMV, doença e doença invasiva foram de 94,1%, 15,6% e 3,1% na era 1 versus 91,1% (p=0,57), 25,7% (p=0,17) e 3,5% (p=0,69) na era 2. O tempo entre o transplante e o início do tratamento, a frequência de uso de Valganciclovir (vs. Ganciclovir IV) e o tempo de tratamento foram significativamente maiores na era 2:29,5 vs. 35 dias (p=0,04), 72,6 vs. 50% (p=0,02) e 28 vs. 21,5 dias (p=0,04) respectivamente. Por outro lado, houve uma frequência menor de recidivas na segunda era: 37,7 vs. 62,5%, p=0,02. Houve uma tendência de redução na frequência de necessidade de filgrastim após a mudança do protocolo, passando de 28,1% para 14,0% (p=0,06). Durante o tratamento antiviral, considerando a carga viral no início do tratamento como referência, houve uma redução de 0,49 log UI/ml ao fim da primeira semana de tratamento (p=0,003) e de 1,02 log UI/ml ao final da segunda (p<0,001). Apesar dessa redução consistente, 68,3% dos pacientes apresentaram redução inferior à 1 log UI/ml durante as primeiras duas semanas de tratamento, e esse comportamento não foi diferente entre as eras. CONCLUSÃO: uma estratégia mais liberal para o início do TP para reduzir os riscos relacionados ao CMV não aumentou a frequência de eventos relacionados ao CMV, mas demonstrou uma tendência de redução à evento adverso relacionado ao antiviral.
OBJECTIVE: To demonstrate that PT initiated from a viral load ≥ 2,500 IU/ml does not increase CMV-related stages in kidney transplant recipients, when compared with the treatment of any positive viremia, but reduces adverse events related to exposure to the antiviral. METHODS: retrospective cohort study that included deceased donor kidney transplant recipients transplanted between July 2012 and February 2020 in the SBIBAE kidney transplant program. On December 1, 2015, the care team changed the CMV viral load limit (RT-PCR) for starting PT from > 180 IU/ml (was 1) to ≥ 2,500 IU/ml (was 2), thus designing an experiment Natural. Follow-up time was up to one year after transplantation. The primary stage was severe leukopenia requiring filgrastim during antiviral treatment and the secondary stages of efficiency were CMV disease or invasive disease and safety against relapse. Numerical variables were compared by Mann-Whitney U test and categorical variables and binary results by X2 test. Furthermore, viral load kinetics during treatment were assessed using generalized equation estimates, with adjustment by the Bonferroni test. RESULTS: Of the 347 patients transplanted during the period, 158 were included in the study. They were 51.9 years old, 57.6% were men, 58.9% were white and underwent the transplant after 4.1 years on dialysis. The donors were 45.0 years old, 19.6% were from expanded discounts, 86.1% were perfused by machine (following static storage) and the cold ischemia time was 33 hours. The accumulated dose of thymoglobulin was 325 mg, distributed in 4 doses; 56.3% had delayed graft function. Using each era's targeting, only 13 patients (8.2%) did not receive treatment for CMV: 21.5% had disease, 3.5% had invasive disease, and the remainder were asymptomatic. Treatment was carried out with Ganciclovir in 32.7% and Valganciclovir in 67.6%. Of the total number of patients, 34 were from era 1 and 124 from era 2, with no differences in the demographics of recipients and donors according to the eras. The frequencies of first CMV infection, disease and invasive disease were 94.1%, 15.6% and 3.1% in era 1 versus 91.1% (p=0.57), 25.7% (p =0.17) and 3.5% (p=0.69) in era 2. The time between transplantation and the start of treatment, the frequency of Valganciclovir use (vs. IV Ganciclovir) and the treatment time were significantly higher in era 2: 29.5 vs. 35 days (p=0.04), 72.6 vs. 50% (p=0.02) and 28 vs. 21.5 days (p=0.04) respectively. On the other hand, there was a lower frequency of recurrences in the second era: 37.7 vs. 62.5%, p=0.02. There was a tendency towards a reduction in the frequency of the need for filtering after the protocol change, from 28.1% to 14.0% (p=0.06). During antiviral treatment, considering the viral load at the beginning of treatment as a reference, there was a reduction of 0.49 log IU/ml at the end of the first week of treatment (p=0.003) and 1.02 log IU/ml at the end of the second (p<0.001). Despite this consistent reduction, 68.3% of patients showed a reduction of less than 1 log IU/ml during the first two weeks of treatment, and this behavior was not different between periods. CONCLUSION: A more liberal strategy for initiating PT to reduce CMV-related risks did not increase the frequency of CMV-related events but demonstrated a trend towards a reduction in antiviral-related adverse events.
OBJECTIVE: To demonstrate that PT initiated from a viral load ≥ 2,500 IU/ml does not increase CMV-related stages in kidney transplant recipients, when compared with the treatment of any positive viremia, but reduces adverse events related to exposure to the antiviral. METHODS: retrospective cohort study that included deceased donor kidney transplant recipients transplanted between July 2012 and February 2020 in the SBIBAE kidney transplant program. On December 1, 2015, the care team changed the CMV viral load limit (RT-PCR) for starting PT from > 180 IU/ml (was 1) to ≥ 2,500 IU/ml (was 2), thus designing an experiment Natural. Follow-up time was up to one year after transplantation. The primary stage was severe leukopenia requiring filgrastim during antiviral treatment and the secondary stages of efficiency were CMV disease or invasive disease and safety against relapse. Numerical variables were compared by Mann-Whitney U test and categorical variables and binary results by X2 test. Furthermore, viral load kinetics during treatment were assessed using generalized equation estimates, with adjustment by the Bonferroni test. RESULTS: Of the 347 patients transplanted during the period, 158 were included in the study. They were 51.9 years old, 57.6% were men, 58.9% were white and underwent the transplant after 4.1 years on dialysis. The donors were 45.0 years old, 19.6% were from expanded discounts, 86.1% were perfused by machine (following static storage) and the cold ischemia time was 33 hours. The accumulated dose of thymoglobulin was 325 mg, distributed in 4 doses; 56.3% had delayed graft function. Using each era's targeting, only 13 patients (8.2%) did not receive treatment for CMV: 21.5% had disease, 3.5% had invasive disease, and the remainder were asymptomatic. Treatment was carried out with Ganciclovir in 32.7% and Valganciclovir in 67.6%. Of the total number of patients, 34 were from era 1 and 124 from era 2, with no differences in the demographics of recipients and donors according to the eras. The frequencies of first CMV infection, disease and invasive disease were 94.1%, 15.6% and 3.1% in era 1 versus 91.1% (p=0.57), 25.7% (p =0.17) and 3.5% (p=0.69) in era 2. The time between transplantation and the start of treatment, the frequency of Valganciclovir use (vs. IV Ganciclovir) and the treatment time were significantly higher in era 2: 29.5 vs. 35 days (p=0.04), 72.6 vs. 50% (p=0.02) and 28 vs. 21.5 days (p=0.04) respectively. On the other hand, there was a lower frequency of recurrences in the second era: 37.7 vs. 62.5%, p=0.02. There was a tendency towards a reduction in the frequency of the need for filtering after the protocol change, from 28.1% to 14.0% (p=0.06). During antiviral treatment, considering the viral load at the beginning of treatment as a reference, there was a reduction of 0.49 log IU/ml at the end of the first week of treatment (p=0.003) and 1.02 log IU/ml at the end of the second (p<0.001). Despite this consistent reduction, 68.3% of patients showed a reduction of less than 1 log IU/ml during the first two weeks of treatment, and this behavior was not different between periods. CONCLUSION: A more liberal strategy for initiating PT to reduce CMV-related risks did not increase the frequency of CMV-related events but demonstrated a trend towards a reduction in antiviral-related adverse events.
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Citação
ROCHA, Ana Kleyce Correia Comparação de dois diferentes níveis de carga viral para início de tratamento antiviral na redução de riscos associados ao citomegalovírus em pacientes transplantados de rim sob estratégia preemptiva. 2024. 96 f. Dissertação (Mestrado em Nefrologia) -Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2024.