American Journal of Transplantation 2008; 8: 2111–2118
Wiley Periodicals Inc.
Prevention of Posttransplant Cytomegalovirus Disease
and Related Outcomes with Valganciclovir:
A Systematic Review
H-Y. Suna , M. M. Wagenerb and N. Singhb, ∗
a
National Taiwan University Hospital and National Taiwan
University College of Medicine, Taipei, Taiwan
b
University of Pittsburgh, Pittsburgh, PA
∗ Corresponding author: Nina Singh, nis5@pitt.edu
The precise impact of valganciclovir as preventive ther-
apy for cytomegalovirus (CMV) in solid organ trans-
plant (SOT) recipients is not fully defined. Data from
studies using valganciclovir as preemptive therapy or
prophylaxis for CMV in SOT recipients were synthe-
sized for descriptive analysis. CMV disease occurred
in 2.6% and 9.9% of the patients receiving valgan-
ciclovir as preemptive therapy and prophylaxis, re-
spectively. Although the incidence of early-onset (≤90
days posttransplant) CMV disease was only 0.8% and
1.2% in all patients and R–/D+ patients receiving val-
ganciclovir prophylaxis, the incidence of late-onset
(>90 days posttransplant) CMV disease rose up to
8.9% and 17.7% in the prophylactic group, respectively.
On the contrary, no patients developed late-onset CMV
disease in preemptive group. Both approaches with
valganciclovir have successfully decreased CMV dis-
ease in SOT recipients. Late-onset CMV disease is
a complication observed uniquely with valganciclovir
prophylaxis, particularly in R–/D+ patients, but not
with preemptive therapy.
Key words: Cytomegalouirus, prevention, transplants,
valganciclovir
Recieved 08 May 2008, revised 03 July 2008 and
accepted for publication 05 July 2008
Introduction
Cytomegalovirus (CMV) is an important opportunistic
pathogen in solid organ transplant (SOT) recipients. In the
absence of any form of preventive therapy, CMV infection
develops in 36–100% of the SOT recipients and symp-
tomatic disease in 11–72% of the patients, most often
during the first 100 days after transplantation (1). Current
antiviral agents and preventive strategies have led to a
decrease in the incidence of CMV disease. Compared to
patients treated with placebo or no antiviral therapy, those
receiving preemptive therapy and prophylaxis have a 72–
80% lower likelihood for the development of CMV disease
C 2008 The Authors
Journal compilation 
C 2008 The American Society of
Transplantation and the American Society of Transplant Surgeons
doi: 10.1111/j.1600-6143.2008.02369.x
(2). Furthermore, reduced allograft rejection, opportunistic
infections and mortality has been documented with the
receipt of prophylaxis (2).
Despite these advances, a number of issues remain unre-
solved (3). Although prophylaxis has effectively prevented
CMV disease in the early posttransplant period, the inci-
dence of late-onset CMV disease occurring after discon-
tinuation of prophylaxis has increased from 0–5% in the
era of long-term use of acyclovir (4,5) to 2.6–7% in patient
receiving prophylaxis with oral ganciclovir (6,7). It has been
proposed that the optimal development of long-term pro-
tective immunity against CMV may be compromised with
the prolonged use of a potent antiviral agent such as gan-
ciclovir (8–11). In addition, indirect sequelae of CMV still
complicate the posttransplant course (12–16).
Valganciclovir has emerged as the preferred antiviral agent
for the prevention of CMV in SOT recipients because
of its oral availability, convenient dosing schedule, and
10-fold higher bioavailability than oral ganciclovir (17). Al-
though not approved by the FDA for prophylaxis in liver
transplant recipients, surveys of CMV prevention strate-
gies after liver and kidney transplantation show that val-
ganciclovir is the most commonly prescribed antiviral
agent for the prevention of CMV (18,19). However, exist-
ing studies have primarily comprised small sample sizes
and previous meta-analyses have excluded valganciclovir
(1,2,20,21). Thus, we performed a review and conducted
a systemic analysis to examine the efficacy of valganci-
clovir as preemptive therapy versus prophylaxis for CMV
disease and CMV-associated indirect outcomes in SOT
recipients.
Methods
English-language reports of published studies utilizing valganciclovir for the
prevention of CMV disease in SOT recipients were identified by cross-
referencing the keywords ‘valganciclovir’ and ‘transplantation’ or ‘trans-
plant’. Data bases searched from March, 2001 when valganciclovir was
approved by the FDA to April, 2008 included PubMed (http://www.ncbi.
nlm.nih.gov), ISI Web of Science (http://www.isiknowledge.com),
ScienceDirect (http://www.sciencedirect.com), the Cochrance Central Reg-
ister of Controlled Trials (http://www.mrw.interscience.wiley.com/cochrane/
cochrane_clcentral_articles_fs.html), EMBASE (http://www.embase.com)
and BIOSIS (http://www.biosis.org). Bibliographies of original articles
were manually reviewed for additional studies. Studies were included if
2111
Sun et al.
Table 1: Characteristics of studies with valganciclovir preemptive therapy for the prevention of CMV diseases
Study design1 (number of studies) Type of transplantation
Randomized controlled (2)
(27)
(32)
Prospective with historical controls (1)
(22)
Prospective without controls (4)
(23)
(26)
(31)
(30)
Sequential cohort study (1)
(28)
Retrospective with concurrent controls (1)
(34)
Retrospective without controls (2)
(29)
(33)
1 Numbers in the column represent reference numbers. Data from two references (22,23) with overlapping study cohorts were analyzed
only once.
2 VAC = valacyclovir; 3 VGC = valganciclovir; 4 GCV = ganciclovir; 5 NA = not available; 6 SOT = solid organ transplant.
valganciclovir was used as preemptive therapy or prophylaxis in SOT recip-
ients. Studies were excluded if (1) they were review articles not reporting
original data; (2) valganciclovir was used as treatment of established CMV
disease; (3) valganciclovir was used for CMV prevention in non- SOT recipi-
ents. Two of the authors independently extracted the data for analyses. Any
discrepancies in data extraction were resolved by review and discussion.
Authors of some original articles were contacted if additional or clarification
of reported results was deemed necessary. Data from one institution with
overlapping study cohorts in two reports were analyzed only once to avoid
patient duplication (22,23).
Preemptive therapy was defined as administration of anti-CMV agent upon
detection of CMV viremia by pp65 antigen or polymerase chain reaction
(PCR) assay (24), and prophylaxis as administration of a course of anti-
CMV agents at the time of or soon after transplantation (7). Late-onset
CMV disease was defined as CMV disease occurring after 90 days post-
transplantation (25). Data regarding transplanted organ, donor and/or recip-
ient CMV serostatus, CMV disease, late-onset CMV disease, time to CMV
disease, T-cell-depleting antibody (alemtuzumab, OKT3 antibodies or an-
tithymocyte globulin) use, recurrence of CMV viremia, antiviral resistance,
rejection, graft loss, opportunistic infections and mortality were collected
for analysis. Data from randomized or cohort studies, with or without a
control group were analyzed and the results were reported in a descriptive
fashion.
Results
Risk of CMV disease with preemptive therapy
Ten studies (two randomized controlled trials, four prospec-
tive studies, three retrospective studies one with concur-
rent control and one cohort study with historic control
group) have described the use of valganciclovir as preemp-
tive therapy (22,23,26–34) (Table 1). The follow-up duration
was a minimum of 12 months after transplantation in all
but three studies (29,30,33). In one report, the proportion
2112
Control groups
Kidney Prophylaxis with VAC2
Kidney Prophylaxis with VGC3
Liver Preemptive therapy with GCV4
Liver NA5
SOT6 NA
SOT NA
SOT NA
Kidney Prophylaxis with VGC
Liver or kidney Preemptive therapy with GCV
Kidney NA
Heart NA
of patients with treatment failure (8.3%, 7/84), defined as
the necessity of valganciclovir change due to any other
cause or recurrent viral detection during the 30 days after
completion of antiviral course was employed as an end-
point (26). Another study reported only the cumulative in-
cidence of CMV disease in patients receiving valganciclovir
as preemptive therapy or as prophylaxis (5.0%, 5/101) (29).
The total number of patients receiving preemptive therapy
with valganciclovir was not reported in one study, how-
ever, none developed CMV disease (33). Thus, the efficacy
of preemptive therapy against CMV disease could be as-
sessed in 7/10 studies (Table 2). Of 761 patients in these
studies, 20 (2.6%) developed CMV disease. CMV disease
comprised viral syndrome in 82.4–100% and tissue inva-
sive disease in 0–17.6% of the patients (27,28,32). Exclu-
sion of a study (28) where only 29 (26%) of the patients had
surveillance monitoring for CMV DNA PCR as proposed
yielded an incidence of CMV disease of 0.5% (3/651)
in SOT recipients receiving valganciclovir as preemptive
therapy.
The proportion of patients with late-onset CMV disease
was reported in three studies; none (0%, 0/20) had late-
onset CMV disease (27,28,32). CMV disease occurred
within 30 days after transplantation in five patients (25%),
and between 30 and 90 days in the other 15 (75%). The in-
cidence of CMV disease in R–/D+ patients base on three
studies was 0% (0/36), 7.7% (1/13) and 33.3% (2/6), re-
spectively (23,27,32). None of these high-risk patients de-
veloped late-onset CMV disease. Of a total of 650 R+
patients in six studies, 17 (2.6%) developed CMV disease
(27,28,30–32). Only two studies explicitly reported receipts
of T-cell-depleting agents (23,28). CMV disease developed
in 15.5% (17/110) of the patients receiving these agents
and 0% (0/187) of those not receiving (23,28).
American Journal of Transplantation 2008; 8: 2111–2118
 Valganciclovir for CMV Prevention

Table 2: Outcomes with valganciclovir as preemptive therapy or prophylaxis

Preemptive therapy Prophylaxis
Variables No. of studies % (n/N)1 Median (range)2 No. of studies % (n/N) Median (range)
CMV disease
Overall rate 7 2.6 (20/761) 0 (0–15.5) 21 9.9 (175/1,767) 8.2 (0–85.7)
R–/D+ patients3 3 5.5 (3/55) 7.7 (0–33.3) 17 20.1 (123/613) 18.8 (0–85.7)
R+ patients3 6 2.6 (17/650) 0 (0–15.5) 14 4.0 (28/699) 2.6 (0–15.9)
Late-onset
Overall 3 0 (0/195) 0 (NA4 ) 16 8.9 (104/1,164) 7.5 (0–85.7)
R–/D+ patients 3 0 (0/55) 0 (NA) 13 17.7 (89/504) 16.3 (0–85.7)
Tissue-invasive 3 15.0 (3/20) 0 (0–17.6) 12 33.9 (41/121) 31.7 (0–100)
Rejection
Incidence 4 10.8 (41/379) 8.7 (6.4–36.1) 10 17.6 (173/985) 15.5 (2.0–42.9)
Graft loss
Incidence 4 3.9 (15/380) 2.4 (1.8–5.9) 8 2.5 (22/870) 2.1 (0–14.3)
Opportunistic infections
Incidence 3 28.5 (77/270) 24.3 (10.2–75.0) 3 7.8 (27/347) 7.5 (0–18.4)
Mortality
Incidence 4 8.2 (31/380) 0.9 (0–15.7) 14 4.4 (50/1,128) 1.9 (0–15.3)
CMV = cytomegalovirus.
1 % = percentage; n = number of patients with positive results; N = total number of patients in the same category.
2 Vales represent median and range of incidence for the reported variables.
3 R–/D+ = recipient-negative/donor-positive CMV serostatus and R+ = recipient-positive CMV serostatus.
4 NA = not available.

Preemptive therapy tool utilized to initiate valganciclovir
was CMV pp65 antigenemia in six studies (54.5%) and
CMV DNA PCR in seven (63.6%). The cut-offs for these
assays to initiate preemptive therapy varied for different
studies. Some studies set criteria of antigenemia for the
initiation of preemptive therapy as ≥1 cell with character-
istic immunofluorescence per 2 × 105 polymorphonuclear
cells (22,23) while others employed ≥20 (29) or >25 of
2 × 105 polymorphonuclear cells to initiate such therapy
(30,31). Similarly, the threshold of DNAemia by CMV DNA
PCR to initiate preemptive treatment varied from ≥15 to
≥2000 copies/mL (23,27–29,32–34). In all, three studies
monitored for antigenemia or DNAemia for 3 months, 2 for
6 months, 2 for 12 months, and 1 for 4 months posttrans-
plant (22,23,26–32). Six studies monitored weekly and two
every 2 weeks.
29–33). Five studies reported subsequent follow-up for
39 patients with recurrence after preemptive valganciclovir
use for their first episodes of viremia (23,27,30–32). Two
patients developed CMV disease (27); one of two did not
have CMV PCR monitoring. Therefore, CMV disease devel-
oped later while DNAemia progressed to CMV disease in
the other patient despite valganciclovir and reduced im-
munosuppression. However, analysis of UL97-gene se-
quencing failed to detect ganciclovir-resistant mutations
and viremia resolved with intravenous ganciclovir (27). Only
one study performed sequencing of the CMV UL97 gene in
patients with recurrence, and none had mutations known
to cause ganciclovir resistance (32). Most patients with
recurrent viremia were successfully treated with a repeat
course of valganciclovir.

Regardless, 329 (35.5%) of 926 patients in preemptive
groups in nine studies had detectable viremia during
surveillance monitoring as per study criteria (22,23,27–
34). Six of the nine studies described explicitly the re-
lationship between preemptive therapy and subsequent
development of CMV disease (22,23,27,30,31,33,34). No
CMV disease occurred after receipt of as preemptive ther-
apy in five studies. In the sixth study, one patient de-
veloped CMV disease 1 day after preemptive therapy
with valganciclovir; the other patient had CMV syndrome
11 days after the diagnosis of CMV DNAemia with subse-
quent noncompliance and missing the next PCR assess-
ment (27). Forty-eight (19.4%) of 248 patients in eight
studies who received valganciclovir as preemptive ther-
apy for CMV infection had recurrent viremia (22,23,26,27,
Risk of CMV disease with prophylaxis
A total of 2094 patients in 25 studies reported valgan-
ciclovir use for CMV prophylaxis (three randomized con-
trolled trials, five prospective studies two with historic
controls, sixteen retrospective two with concurrent and
five with historic control and one cohort study with historic
control group) (28,31,32,35–56) (Table 3). One study where
valganciclovir use was preceded by intravenous ganciclovir
for 30 days in all patients and for 90 days in R–/D+ pa-
tients was excluded (49). Treatment duration varied from
14 to 240 days, but most of the patients received valganci-
clovir for at least 90–100 days. The efficacy of valganciclovir
for the prevention of CMV disease was reported in the
21 studies comprising a total of 1767 patients. CMV dis-
ease developed in 175 (9.9%) with follow-up duration over

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Sun et al.

Table 3: Characteristics of studies with valganciclovir prophylaxis for the prevention of CMV diseases
Study design1 (number of studies) Type of transplantation Control groups
Randomized controlled (3)
(39) Kidney Prophylaxis with GCV2
(32) Kidney Preemptive therapy with VGC3
(44) Solid organ transplant Prophylaxis with GCV
Prospective with historical controls (1)
(42) Lung Prophylaxis with GCV
Prospective without controls (3)
(31) Solid organ transplant NA4
(37) Solid organ transplant NA
(47) Solid organ transplant NA
Sequential cohort study (1)
(28) Kidney Preemptive therapy with VGC
Retrospective with concurrent controls (2)
(54) Liver Prophylaxis with GCV
(45) Kidney; kidney–pancreas Prophylaxis with GCV
Retrospective with historical controls (5)
(35) Liver Prophylaxis with GCV
(55) Heart Prophylaxis with GCV
(36) Kidney or/and pancreas Prophylaxis with GCV
(40) Liver Prophylaxis with GCV
(48) Kidney or pancreas Prophylaxis with GCV
Retrospective without controls (9)
(56) Heart NA
(53) Kidney NA
(38) Liver NA
(41) Liver NA
(43) Kidney NA
(46) Kidney or/and pancreas NA
(50) Kidney–pancreas NA
(51) Liver NA
(52) Kidney NA
1 Numbers in the column represent reference numbers.
2 GCV = ganciclovir; 3 VGC = valganciclovir; 4 NA = not available.

1 year (28,31,32,35–48,50–52,56) (Table 2). Of 148 patients
with CMV disease in 16 studies, 117 (79%) were R–/D+
(28,32,35,37,38,40–47,50,52,56). CMV disease consisted
of viral syndrome in 66.1% (80/121) and tissue invasive
disease in 33.9% (41/121) in 12 studies with data avail-
able (28,32,38,40–44,46,47,52,56). All episodes of CMV
disease were due to viral syndrome in 4/12 studies and
due to tissue invasive disease in one. In the remaining
seven studies, 40–82.8% of CMV disease was due to viral
syndrome and 17.2–60% due to tissue invasive disease.
CMV disease developed a median of 151 days posttrans-
plant (range, 20–312 days) in 20 patients with data avail-
able (32,38,40,43,46,52). Three of the 20 patients devel-
oped CMV disease within 90 days, that is, on 20, 60
and 82 days; CMV occurred after 90 days in the remain-
ing 17 patients (38,43). In all, 104/113 (92.0%) patients
with CMV disease developed late-onset CMV disease in
16 studies with data available (28,31,32,35,37,38,40,42–
47,50,51,56). The incidence of early-onset CMV disease
was 0.8% (9/1164), and that of late-onset CMV disease
was 8.9% (104/1164). Excluding the two studies in which
prophylaxis was used for more than 90–100 days, the inci-
dence of late-onset CMV was 10.2%. Four of the 16 stud-
ies had cases of breakthrough CMV disease under prophy-
laxis use, but none contributed to the cases of late-onset
CMV disease (28,38,43,44). The duration from transplan-
tation to development of late-onset CMV disease was a
median of 152 days (range 114–312 days).
In the 10 studies that considered ganciclovir-resistance,
five assessed if resistant virus existed by clinical observa-
tion and none was documented (35,45,48,52,53). PV16000
trial detected ganciclovir-resistant virus by UL97-gene se-
quencing in none of the patients receiving valganciclovir
on day 100 posttransplantation (0%, 0/198) and also in
none of those receiving valganciclovir and with suspicion
of CMV disease (0%, 0/55) (44,57). One study performed
genotypic resistance testing in all patients with detectable
viremia after prophylaxis, and two patients receiving val-
ganciclovir had ganciclovir-resistant virus (42). In the re-
maining three studies (36,54,55), patients were assessed
for ganciclovir-resistant CMV as clinical indicated and one
patient had documented resistant virus (54).
Seventeen studies enrolled a total of 613 R–/D+ pa-
tients receiving valganciclovir as prophylaxis. Of there,
123 (20.1%) developed CMV disease (28,32,35,37,38,

2114 American Journal of Transplantation 2008; 8: 2111–2118


40–47,50,52,53,56) (Table 2). In 13 studies with data avail-
able, the incidence of early-onset CMV disease in R–/D+
patients was 1.2% (6/504) and that of late-onset was
17.7% (89/504). Additionally, 14 studies evaluated a total
of 699 R+ patients, and 28 (4.0%) of them had CMV dis-
ease (28,31,32,38–40,42,43,45–47,50–52). Thirteen stud-
ies reported the onset of CMV disease in R+ patient; the
incidence of early-onset CMV disease was 0.5% (3/630)
and that of late-onset was 2.2% (14/630). CMV disease
developed in 4.7% (16/399) of the patients who received
T-cell-depleting agents in five studies with data available
(28,31,45,47,50) and in 16.5% (54/328) of those not re-
ceiving these agents in four studies (35,40,41,56).
Rejection
Four studies reported the overall rejection rate of 10.8%
(41 patients) in a total of 379 patients receiving preemp-
tive therapy (23,27,28,32). The overall rejection was 17.6%
(173/985) in the 10 prophylactic studies with data available
(28,31,32,36,39,40,44,46,50,56).
Graft loss
Fifteen patients (3.9%) of 380 patients in preemptive
group had graft loss in four studies with data avail-
able (23,27,28,32). Eight prophylactic studies described
the number of patients with graft loss, and the overall rate
was 2.5% (22/870) (28,32,36,39,44,46,48,56).
Opportunistic infections
Three preemptive studies reported the proportion of
study population that developed opportunistic infections
(23,27,32). A total of 270 patients were enrolled in these
three studies, and 77 (28.5%) developed opportunistic in-
fections. Three prophylactic studies reported the propor-
tion of patients with opportunistic infections, and the over-
all rate was 7.8% (27/347) (32,44,53).
Mortality
The overall mortality rate was 8.2% (31/380) from four
preemptive studies with reported data (23,27,28,32).
The mortality in 14 prophylactic studies with re-
ported data was 4.4% (50/1,128) (28,31,32,36–
38,40,42,44,46,48,53,55,56).
Discussion
Evidence-based systematic synthesis of published data in
our study shows that the overall incidence of CMV disease
in patients receiving valganciclovir prophylaxis was 9.9%.
Ninety-two percent of the patients with CMV disease in the
prophylactic group had late-onset disease. The incidence
of CMV disease in patients receiving valganciclovir as pre-
emptive therapy was 2.6%. Late-onset CMV disease was
not observed in this group. Compared with the preemptive
therapy and prophylaxis with ganciclovir in a meta-analysis
(21), the prevention of CMV disease with valganciclovir ef-
American Journal of Transplantation 2008; 8: 2111–2118
Valganciclovir for CMV Prevention
fectively decreased the incidence of CMV disease in SOT.
However, the characteristics of CMV disease have evolved
in the current era. Most CMV disease with the use of an-
tiviral prophylaxis presents as late-onset CMV disease and
occurs a median of 152 days after transplantation.
Optimal prevention of CMV is particularly relevant in R–/D+
patients given substantial morbidity associated with CMV
in these patients (58,59). Existing guidelines recommend
antiviral prophylaxis for the prevention of CMV disease in
R–/D+ patients (60,61). The overall incidence of CMV dis-
ease, and of late-onset CMV disease in R–/D+ patients
receiving prophylaxis was 20% and 18%, respectively. In
contrast, all CMV disease in R–/D+ subgroups receiving
preemptive therapy occurred within 90 days of transplan-
tation. Thus, the data show that R–/D+ patients receiving
prophylaxis are uniquely susceptible to the development of
CMV disease in the late posttransplant period. Prior stud-
ies have documented late-onset CMV disease in 18–26%
of R–/D+ SOT patients receiving ganciclovir prophylaxis
(6,40,44,62,63). Furthermore, late-onset CMV disease has
been shown to be an independently significant predictor of
mortality during the first posttransplant year (6,54). Thus,
the use of valganciclovir as prophylactic strategy may not
be wholly adequate for preventing CMV disease in R–/D+
patients.
Compared with the patients receiving preemptive therapy
and prophylaxis with ganciclovir in a previous meta-
analysis (21), the patients receiving valganciclovir in this
study had lower overall incidence of CMV disease both
in the prophylactic (9.9%) and preemptive groups (2.6%).
Furthermore, the incidence of rejection, graft loss and
mortality in the patients in this study was also lower
than those reported with the use of ganciclovir (21).
Such reduced risk of CMV disease and CMV-associated
indirect outcomes in this study might be attributable to
the improvement in transplant patient care, advances in
immunosuppressive therapy and wider availability of rapid
and reliable diagnostic tools for CMV.
Several limitations of this review deserve to be acknowl-
edged. Data regarding CMV disease and other outcomes
are reported in a descriptive fashion only without compar-
ative statistical analysis. Statistical comparisons of pooled
data from various studies are not considered scientifically
appropriate unless comparable groups or the same type
of patient population are compared. For example, if some
studies included more high-risk patients (R–/D+), the per-
centage of disease could be higher than in studies that
included largely low-risk patients. Statistical analysis on
summed data therefore could lead to erroneous conclu-
sions. There were far fewer studies of preemptive therapy
in the literature, and most studies were from single cen-
ters with small sizes. A meta-analysis by definition is a
combination of multiple studies that address a research
related hypothesis. In theory, combining multiple studies
attempts to overcome the limitation of statistical power
2115
Sun et al.
associated with small sample sizes in individual studies.
However, given the paucity of randomized controlled stud-
ies for the prevention of CMV with valganciclovir, it is not
possible to perform a meta-analysis for our study. In ad-
dition, several factors with potential to compromise the
findings of this study exists, such as different CMV serosta-
tus in study populations, lack of uniform diagnostic criteria
for indirect effects of CMV and variability in valganciclovir
dosage used. Nevertheless, valganciclovir is the most com-
monly prescribed antiviral agent for CMV prevention nowa-
days (18,19), and our study offers the most relevant and
comprehensive information regarding its use for CMV pre-
vention in SOT patients.
In summary, preemptive and prophylactic strategy with val-
ganciclovir use has successfully decreased the incidence
of posttransplant CMV disease in SOT patients. However,
most patients, in particular those belonging to the R–/D+
group with CMV disease in the current era present with
late-onset CMV disease. Prophylaxis is uniquely associated
with late-onset disease while preemptive therapy approach
is protective against late-disease. Future studies should
focus on head to head comparison between preemptive
therapy and prophylaxis for the prevention of CMV dis-
ease and clearly assess the efficacy of different preventive
strategies for the indirect outcomes associated with CMV
infection. Optimal approach is the one that has a protec-
tive effect on both CMV disease and indirect outcomes or
tips the balance in favor of achieving best outcomes after
transplantation.
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