Role of Secondary Prophylaxis with Valganciclovir in the Prevention of Recurrent Cytomegalovirus Disease in Solid Organ Transplant Recipients

Gardiner, Bradley J.; Chow, Jennifer; Price, Lori Lyn; Nierenberg, Natalie; Kent, David M.; Snydman, David R.

doi:10.1093/ofid/ofx163.1914

Cited by 16 publications

(35 citation statements)

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“…Of note, the duration of DNAemia was nearly identical in the two groups which argues against selection bias. Although this observation has been previously reported in solid organ transplant (SOT) recipients, [9][10][11] to the best of our knowledge this is the first study demonstrating the lack of benefit of CMV maintenance therapy in HCT recipients. The recurrence rate while off therapy in this cohort of allogeneic HCT recipients (73%) was higher than that reported in the published studies in SOT population with recurrence rates ranging from 23% to 33%.…”

Section: Discussionmentioning

confidence: 57%

“…The recurrence rate while off therapy in this cohort of allogeneic HCT recipients (73%) was higher than that reported in the published studies in SOT population with recurrence rates ranging from 23% to 33%. 9,10,[12][13][14][15][16] In SOT patients, secondary prophylaxis does not lead to long-term protection and in fact cell-mediated immunity may better predict the likelihood of recurrence of CMV. 10,17 We observed that without exception all the patients with symptomatic CMV disease during the initial CMV viremia experienced recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…9,10,[12][13][14][15][16] In SOT patients, secondary prophylaxis does not lead to long-term protection and in fact cell-mediated immunity may better predict the likelihood of recurrence of CMV. 10,17 We observed that without exception all the patients with symptomatic CMV disease during the initial CMV viremia experienced recurrence. Since we previously reported a stepwise increase in CMV DNA levels for patients with asymptomatic viremia, CMV syndrome and tissue-invasive disease, respectively, 7 it is possible that early initiation of preemptive antiviral therapy could reduce the risk of recurrence, a hypothesis that requires further study.…”

Section: Discussionmentioning

confidence: 99%

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Use of maintenance therapy and incidence of recurrent Cytomegalovirus DNAemia among allogeneic hematopoietic cell transplant recipients

Camargo

Anderson

Rosa

et al. 2019

Transplant Infectious Dis

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Background Cytomegalovirus (CMV) infection is the most common infection following hematopoietic cell transplantation (HCT). Preemptive antiviral therapy is highly effective at halting viral replication and preventing CMV disease; however, recurrence rates after clearance of CMV DNAemia are high (50‐70%). Current treatment guidelines recommend maintenance therapy after initial clearance. Yet, the effectiveness of this intervention to prevent recurrence is not well defined. Objectives We aimed to assess the impact of maintenance therapy on the probability of recurrent CMV in allogeneic HCT recipients with early CMV reactivation. Study design Sixty‐six patients with an initial episode of early CMV reactivation who achieved viral clearance in response to preemptive therapy were included. We compared the incidence of recurrent CMV DNAemia in patients who received maintenance therapy vs those who underwent early discontinuation of antiviral therapy. Results Recurrence occurred in 47/64 (73%) patients, including 11/14 (79%) patients without maintenance therapy and 36/50 (72%) of patients who received maintenance therapy (P = 0.74). The propensity score adjusted risk ratio for the effect of maintenance therapy on recurrence was 0.89 (95% CI 0.64‐1.25; P = 0.41). In a time to event analysis using the unweighted cohort, the 90‐day probability of CMV recurrence was similar between patient groups independent of maintenance therapy administration (54% vs 64% for maintenance vs non‐maintenance groups, respectively; log‐rank P = 0.37). Conclusion These data suggest that maintenance antiviral therapy does not reduce the incidence of CMV recurrence while off therapy and is of limited value in HCT recipients who have successfully eradicated CMV DNAemia in response to preemptive therapy. Larger studies in this area are needed.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Use of maintenance therapy and incidence of recurrent Cytomegalovirus DNAemia among allogeneic hematopoietic cell transplant recipients

Camargo

Anderson

Rosa

et al. 2019

Transplant Infectious Dis

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“…However, post‐prophylaxis (late‐onset) CMV reactivation still occurs, contributing to graft loss and premature death via its direct and indirect effects . Recurrent disease occurs in up to 30% of patients despite successful treatment for CMV, and while significant efforts have been made to identify risk factors for relapse and implement strategies to reduce it, these seem to have had minimal impact on recurrence rates . While it is clear from prior studies that patients who develop CMV disease have a higher risk of death than those who do not, the impact of recurrent disease on survival is less well characterized.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously shown that secondary prophylaxis delays but do not prevent relapse, and that low absolute lymphocyte count at the time of CMV treatment completion is associated with recurrence . The aim of this study was to explore the impact of recurrent CMV infection on long‐term survival in a retrospective cohort of heart, liver, and kidney transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

The impact of recurrent cytomegalovirus infection on long‐term survival in solid organ transplant recipients

Gardiner

Chow

Brilleman

et al. 2019

Transplant Infectious Dis

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Background: Cytomegalovirus (CMV) remains a significant contributor to morbidity and mortality following solid organ transplantation (SOT). While recurrent infection occurs in up to 30% of patients, its impact on mortality is unclear. The aim of this study was to explore the relationship between recurrent CMV infection and longterm survival in SOT recipients. Methods:We performed a retrospective cohort study of SOT recipients who completed treatment for an episode of CMV infection. Patients were followed until death, loss to follow-up or 10 years following CMV treatment completion. Univariable and multivariable hazard ratios (HR) were calculated, treating relapse and rejection following CMV as time-varying. Results: About 79 kidney, 52 heart, 34 liver, and 5 liver-kidney transplant recipients were included. About 62/170 died, at a median of 3.8 years (IQR 0.8-6.6 years). Median follow-up among the 108 survivors was 7.4 years (IQR 3.7-10 years). Recurrent CMV infection occurred in 49/170 (29%), 67% within 6 months of treatment completion.Mortality among those who relapsed was 39% (19/49) vs 36% (43/121) in those who remained relapse-free (unadjusted HR 1.59, 95% CI 0.92-2.75, P = .10). After adjusting for age and transplanted organ, findings were similar (HR 1.68, 95% CI 0.93-3.04, P = .09). Conclusions: Mortality following CMV remains high even in the valganciclovir era.Although our findings suggest a possible increased risk of death among patients with recurrent CMV, these did not reach statistical significance. The complex nature of these patients, multiple potential confounders, and limited statistical power made detection of small effects difficult. Larger prospective studies evaluating the clinical impact of strategies to reduce recurrence are needed. K E Y W O R D S recurrent cytomegalovirus, survival, transplant S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Gardiner BJ, Chow JK, Brilleman SL, Peleg AY, Snydman DR. The impact of recurrent cytomegalovirus infection on long-term survival in solid organ transplant recipients. Transpl Infect Dis.

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Viral disease of the year: Anterior uveitis

Griffiths¹

2018

Reviews in Medical Virology

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Role of Secondary Prophylaxis with Valganciclovir in the Prevention of Recurrent Cytomegalovirus Disease in Solid Organ Transplant Recipients

Cited by 16 publications

References 0 publications

Use of maintenance therapy and incidence of recurrent Cytomegalovirus DNAemia among allogeneic hematopoietic cell transplant recipients

Use of maintenance therapy and incidence of recurrent Cytomegalovirus DNAemia among allogeneic hematopoietic cell transplant recipients

The impact of recurrent cytomegalovirus infection on long‐term survival in solid organ transplant recipients

Viral disease of the year: Anterior uveitis

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