A Randomized Prospective Trial of Oral Versus Intravenous Ganciclovir for Prophylaxis of Cytomegalovirus Infection and Disease in High-Risk Kidney Recipients

SummaryCytomegalovirus is the most important pathogen causing opportunistic infections in kidney allograft recipients. The occurrence of CMV disease is associated with higher morbidity, higher incidence of other opportunistic infections, allograft loss and death. Therefore, an efficient strategy to prevent CMV disease after kidney transplantation is required. Two options are currently available: pre-emptive therapy based on regular CMV PCR monitoring and generalized antiviral prophylaxis during a defined period. In this review, we describe those two approaches, highlight the distinct advantages and risks of each strategy and summarize the four randomized controlled trials performed in this field so far. Taken this evidence together, pre-emptive therapy and anti-CMV prophylaxis are both equally potent in preventing CMV-associated complications; however, the pre-emptive approach may have distinct advantages in allowing for development of long-term anti-CMV immunity. We propose a risk-adapted use of these approaches based on serostatus, immunosuppressive therapy and availability of resources at a particular transplant centre. Cytomegalovirus in kidney transplantationGeneral introduction Cytomegalovirus (CMV) is the most important viral pathogen and the most prevalent opportunistic infection after kidney transplantation [1]. Infection occurs by three ways (in order of incidence): (i) endogenous reactivation of CMV in the recipient, (ii) donor-derived infection transmitted by the allograft and (iii) de novo infection acquired from the general population. From a clinical point of view, three distinctive presentations can occur: asymptomatic viraemia, CMV viral syndrome (with fever, malaise and leukopenia) and CMV tissue invasive disease (with documented end-organ damage in histology or imaging such as colitis, hepatitis, pneumonitis or retinitis).Apart from CMV viral syndrome and tissue invasive disease, a number of indirect immunomodulatory effects of CMV have been postulated [2], thereby increasing the incidence of acute and chronic rejection after solid organ transplantation on one side (probably via a bystander activation of alloreactive T cells during an antiviral response of the host), but also the incidence of other opportunistic infections on the other side. Immunity against CMVThe incidence of CMV infection and serious clinical complications is highly dependent on the serostatus (presence of CMV-specific antibodies) of recipient (R) and donor (D) with the constellation D+RÀ bearing the highest risk, followed by D+R+, DÀR+ and DÀRÀ. Studies on anti-CMV strategies usually distinguish between these risk categories, thereby often summarizing the D+R+ and DÀR+ groups in an intermediate-risk category [3]. The DÀRÀ recipients as ©

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“…Equal or improved efficacy of oral valganciclovir in comparison with intravenous ganciclovir was later demonstrated in two randomized trials .…”

Section: Prophylaxis Against CMV Infection or Reactivationmentioning

confidence: 99%

Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy?

2015

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“…Although oral GC is not currently available to any further extent in current practice, we found a potential benefit of GC even though most studies were conducted on oral forms. Thus, we predict that IV GC may be more efficacious than oral GC because of higher bioavailability and serum concentration under therapeutic dose [ 71 , 72 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of conventional antiviral agents in preventive strategies for cytomegalovirus infection after kidney transplantation: a systematic review and network meta‐analysis

Ruenroengbun

Numthavaj

Sapankaew

et al. 2021

Transplant International

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Summary Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral‐agents are used as universal prophylaxis. Our purpose aimed to compare and rank efficacy and safety. MEDLINE, Embase, SCOPUS, and CENTRAL were used from inception to September 2020 regardless language restriction. We included randomized clinical trials (RCTs) comparing the CMV infection/disease prophylaxis among antiviral‐agents in adult KT recipients. Of 24 eligible RCTs, prophylactic valganciclovir (VGC) could significantly lower the overall CMV infection and disease risks than placebo with pooled risk differences (RDs) [95% confidence interval (CI)] of −0.36 (−0.54, −0.18) and −0.28 (−0.48, −0.08), respectively. Valacyclovir (VAC) and ganciclovir (GC) significantly decreased risks with the corresponding RDs of −0.25 (−0.32, −0.19) and −0.30 (−0.37, −0.22) for CMV infection and −0.26 (−0.40, −0.12) and −0.22 (−0.31, −0.12) for CMV disease. For subgroup analysis by seropositive‐donor and seronegative‐recipient (D+/R−), VGC and GC significantly lowered the risk of CMV infection/disease with RDs of −0.42 (−0.84, −0.01) and −0.35 (−0.60, −0.12). For pre‐emptive strategies, GC lowered the incidence of CMV disease significantly with pooled RDs of −0.33 (−0.47, −0.19). VGC may be the best in prophylaxis of CMV infection/disease follow by GC. VAC might be an alternative where VGC and GC are not available.

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Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients

Hodson

Craig

Strippoli

et al. 2008

Cochrane Database of Systematic Reviews

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Cochrane Database of Systematic Reviews Main resultsThirty two trials (3737 participants) were identified. Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 trials; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 trials; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 trials; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (seven trials; RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduced the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but not fungal infection, acute rejection or gra loss. Meta-regression showed no significant di erence in the risk of CMV disease or allcause mortality by organ transplanted or CMV serostatus; no conclusions were possible for CMV negative recipients of negative organs. In direct comparison trials, ganciclovir was more e ective than aciclovir in preventing CMV disease (seven trials; RR 0.37, 95% Cl 0.23 to 0.60).Valganciclovir and intravenous ganciclovir were as e ective as oral ganciclovir. Authors' conclusionsProphylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. They should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants.

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A Randomized Prospective Trial of Oral Versus Intravenous Ganciclovir for Prophylaxis of Cytomegalovirus Infection and Disease in High-Risk Kidney Recipients

Cited by 11 publications

References 10 publications

Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy?

Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy?

Efficacy and safety of conventional antiviral agents in preventive strategies for cytomegalovirus infection after kidney transplantation: a systematic review and network meta‐analysis

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients

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