Análise de diferentes pontos de corte de carga viral para suspender o tratamento do citomegalovírus em receptores de transplante renal sob estratégia preemptiva
Data
2024-10-13
Autores
Miehrig, Arthur Heinz 
Orientadores
Lucio, Roberto Requião Moura
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Avaliar dois diferentes pontos de corte de carga viral (CV) para suspender a medicação antiviral durante o tratamento da infecção pelo citomegalovírus (CMV) em receptores de transplante de rim (RTR) sob estratégia preemptiva. Métodos: estudo de coorte retrospectiva, incluindo RTR CMV IgG+, transplantados entre março/2018 a julho/2020 no Hospital do Rim, que receberam indução timoglobulina, e manutenção com tacrolimo, micofenolato e prednisona. A estratégia preemptiva foi utilizada para redução de riscos, com monitoramento semanal de CV por PCR e tratamento com ganciclovir EV se CV>5.000 UI/ml, ou se CMV doença. Até agosto/2019, o antiviral era interrompido com a supressão completa da CV (grupo 1, n=664) e após essa data o ponto de corte para suspensão foi modificado para < 200 UI/ml (grupo 2, n=384). Desfecho primário: recidiva de CMV, definida como necessidade de retratamento. Desfechos secundários: taxa de infecção e doença pelo CMV e função renal ao final de um ano (TFGe, CKD-EPI). As variáveis associadas com as chances de recidiva foram avaliadas por regressão de Cox. A TFGe foi avaliada ao longo do tempo por estimativas de equação generalizada e ajustadas por Bonferroni. Resultados: Na comparação entre os grupos, os pacientes no grupo 1 eram com mais frequência brancos (55,7 vs. 41,9%, p<0,001) e portadores do vírus C (4,1 vs. 1,85%, p=0,048) e com menos frequência do vírus B (0.6 vs. 2,3%, p=0,01); os doadores eram mais jovens (52 vs. 54 anos, p=0,003), com menos frequência eram doadores falecidos (90,2 vs. 94,3%, p=0,02), de morte cerebrovascular (68,1 vs. 71,3%, p=0,01) e com histórico de hipertensão (40,7 vs. 50,8%, p=0,001). Não houve diferenças nas outras variáveis. As taxas de infecção assintomática foram semelhantes (30,1 vs. 31,3%, p=0,70), mas houve uma tendência de menos doença pelo CMV no grupo 2 (20,3 vs. 15,6%, p=0,06), e uma redução significativa do tempo de tratamento de 27 para 23 dias, p<0,001. A frequência de recidivas foi semelhante (12,2 vs. 10,8%, p=0,24), não havendo diferença nos espectros de infecção e doença (p=0,34). A TFGe ao longo do primeiro ano foi em média 3,84 (IC95%=1,38 a 6,29) ml/min maior no grupo 1 (p=0,002), alcançando 52,6 e 48,9 ml/min no grupo 1 e 2, respectivamente. Entre os 515 pacientes que necessitaram de tratamento de um primeiro evento relacionado ao CMV (infecção ou doença), 119 apresentaram critério para um segundo tratamento, com uma frequência de recidiva de 23,1% (11,3% do total). As variáveis associadas com a probabilidade de recidiva foram: idade do doador (HR=1,024; IC95%= 1,008-1,041) e o tempo de ocorrência do primeiro evento relacionado ao CMV (HR= 0.968; IC95%= 0,956-0,979; p<0,001). Conclusão: a redução da CV do CMV para a interrupção do tratamento antiviral na estratégia preemptiva não aumentou o risco de recidiva, mas houve redução significativa no tempo de tratamento, sem impactos nos espectros da infecção.
Objective: To evaluate two different viral load (VL) thresholds for discontinuing antiviral medication during cytomegalovirus (CMV) infection treatment in kidney transplant recipients (KTR) under a preemptive strategy. Methods: This retrospective cohort study included KTR CMV IgG+, transplanted between March 2018 and July 2020 at the Kidney Hospital, who received thymoglobulin induction and maintenance with tacrolimus, mycophenolate, and prednisone. The preemptive strategy was employed to reduce risks, with weekly VL monitoring by PCR and treatment with intravenous ganciclovir if VL>5,000 IU/ml, or in the presence of CMV disease. Until August 2019, antiviral therapy was discontinued after complete VL suppression (Group 1, n=664), and after this date, the discontinuation threshold was modified to <200 IU/ml (Group 2, n=384). The primary outcome was CMV recurrence, defined as the need for retreatment. Secondary outcomes included CMV infection and disease rates, and renal function at one year (eGFR, CKD-EPI). Variables associated with the recurrence probability were evaluated by Cox regression, and model performance was assessed by area under the ROC curve (AU-ROC). eGFR was assessed over time using generalized equation estimates and adjusted for Bonferroni correction. Results: Compared between groups, patients in Group 1 were more frequently White (55.7% vs. 41.9%, p<0.001) and C virus carriers (4.1% vs. 1.85%, p=0.048), and less frequently B virus carriers (0.6% vs. 2.3%, p=0.01); donors were younger (52 vs. 54 years, p=0.003), less frequently deceased (90.2% vs. 94.3%, p=0.02), cerebrovascular death (68.1% vs. 71.3%, p=0.01), and with a history of hypertension (40.7% vs. 50.8%, p=0.001). No differences were found in other variables. Asymptomatic infection rates were similar (30.1% vs. 31.3%, p=0.70), but there was a trend towards less CMV disease in Group 2 (20.3% vs. 15.6%, p=0.06), and a significant reduction in treatment duration from 27 to 24 days, p<0.001. Recurrence rates were similar (12.2% vs. 10.8%, p=0.24), with no differences in infection and disease spectra (p=0.34). eGFR over the first year was on average 3.84 (95% CI=1.38 to 6.29) ml/min higher in Group 1 (p=0.002), reaching 52.6 and 48.9 ml/min in Groups 1 and 2, respectively. Among the 515 patients who required treatment for a first CMV-related event (infection or disease), 119 met the criteria for a second treatment, with a recurrence rate of 23.1% (11.3% of the total). The variables associated with the likelihood of recurrence were donor age (HR=1.024; 95% CI=1.008-1.041) and the timing of the first CMV-related event (HR=0.968; 95% CI=0.956-0.979; p<0.001). Conclusion: Reducing the CMV VL threshold for discontinuing antiviral treatment in the preemptive strategy did not increase the risk of recurrence but resulted in a significant reduction in treatment duration, with no impact on infection spectra.
Objective: To evaluate two different viral load (VL) thresholds for discontinuing antiviral medication during cytomegalovirus (CMV) infection treatment in kidney transplant recipients (KTR) under a preemptive strategy. Methods: This retrospective cohort study included KTR CMV IgG+, transplanted between March 2018 and July 2020 at the Kidney Hospital, who received thymoglobulin induction and maintenance with tacrolimus, mycophenolate, and prednisone. The preemptive strategy was employed to reduce risks, with weekly VL monitoring by PCR and treatment with intravenous ganciclovir if VL>5,000 IU/ml, or in the presence of CMV disease. Until August 2019, antiviral therapy was discontinued after complete VL suppression (Group 1, n=664), and after this date, the discontinuation threshold was modified to <200 IU/ml (Group 2, n=384). The primary outcome was CMV recurrence, defined as the need for retreatment. Secondary outcomes included CMV infection and disease rates, and renal function at one year (eGFR, CKD-EPI). Variables associated with the recurrence probability were evaluated by Cox regression, and model performance was assessed by area under the ROC curve (AU-ROC). eGFR was assessed over time using generalized equation estimates and adjusted for Bonferroni correction. Results: Compared between groups, patients in Group 1 were more frequently White (55.7% vs. 41.9%, p<0.001) and C virus carriers (4.1% vs. 1.85%, p=0.048), and less frequently B virus carriers (0.6% vs. 2.3%, p=0.01); donors were younger (52 vs. 54 years, p=0.003), less frequently deceased (90.2% vs. 94.3%, p=0.02), cerebrovascular death (68.1% vs. 71.3%, p=0.01), and with a history of hypertension (40.7% vs. 50.8%, p=0.001). No differences were found in other variables. Asymptomatic infection rates were similar (30.1% vs. 31.3%, p=0.70), but there was a trend towards less CMV disease in Group 2 (20.3% vs. 15.6%, p=0.06), and a significant reduction in treatment duration from 27 to 24 days, p<0.001. Recurrence rates were similar (12.2% vs. 10.8%, p=0.24), with no differences in infection and disease spectra (p=0.34). eGFR over the first year was on average 3.84 (95% CI=1.38 to 6.29) ml/min higher in Group 1 (p=0.002), reaching 52.6 and 48.9 ml/min in Groups 1 and 2, respectively. Among the 515 patients who required treatment for a first CMV-related event (infection or disease), 119 met the criteria for a second treatment, with a recurrence rate of 23.1% (11.3% of the total). The variables associated with the likelihood of recurrence were donor age (HR=1.024; 95% CI=1.008-1.041) and the timing of the first CMV-related event (HR=0.968; 95% CI=0.956-0.979; p<0.001). Conclusion: Reducing the CMV VL threshold for discontinuing antiviral treatment in the preemptive strategy did not increase the risk of recurrence but resulted in a significant reduction in treatment duration, with no impact on infection spectra.
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Citação
MIEHRIG, Arthur Heins. Análise de diferentes pontos de corte de carga viral para suspender o tratamento do citomegalovírus em receptores de transplante renal sob estratégia preemptiva. 101 f. Dissertação (Mestrado em Nefrologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.