# Kidney transplant Preemptive therapy or Prophylaxis (KPoP) for CMVPreventionin D+R- Recipients

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $1,254,477

## Abstract

In kidney transplant recipients (KTR), cytomegalovirus (CMV) increases short- and long-term morbidity,
mortality, and allograft failure, mainly due to limitations in current preventive strategies. ~90% of CMV disease
occurs in the ~20% of recipients who are CMV seronegative (R-) and receive of an organ from a CMV
seropositive donor (D+) [D+R-], and results from immune-suppression-impaired development of protective
CMV-specific immune responses. The strategies for CMV prevention in D+R- KTR are Antiviral Prophylaxis
[AP] (suppressive antiviral drug [valganciclovir [VALGAN] or letermovir [LET] given for 200d), and Preemptive
Therapy [PET] (CMV DNAemia is monitored by sensitive quantitative PCR (qPCR) for 100d and VALGAN is
given only to those with CMV DNAemia. AP is used by >90% of centers due to a smaller evidence base for
PET (especially with ATG use) and uncertainty about other long-term outcomes with PET vs AP. In CMV D+R-
liver txp, a randomized clinical trial (RCT) showed that PET was feasible (>90% adherence), reduced antiviral
drug days by ~40% (62d vs. 100d), increased protective CMV-specific immunity (multifunctional CD4/CD8 T-
cells, NK cells, and neutralizing antibody [nAb]) and decreased CMV disease by >50% vs. AP. These results
cannot be directly extrapolated to KTR due to important differences between liver and kidney txp, including the
intensity of immunosuppression and different established/approved prophylaxis regimens. As a result, despite
potential advantages, use of PET in D+R- KTR remains minimal. The long-term goals are to reduce the
negative impact of CMV in D+R- SOT by harnessing CMV-specific immunity, to define CMV immune correlates
for future immune-based preventive strategies, and to provide high-quality evidence to change clinical
practice. The central hypothesis is that PET, compared to AP, through permissive viral replication and
associated antigen exposure-mediated immune priming, leads to increased CMV-specific humoral and cellular
immune responses that result in lower CMV disease incidence in high-risk D+R- KTR. The Specific Aims are
1) To compare PET and AP in D+R- KTR for the prevention of Endpoint Committee confirmed CMV disease by
1-year post-txp (primary endpoint) and longer-term outcomes (graft and patient survival, biopsy-proven acute
allograft rejection, and eGFR by end of follow-up (secondary endpoints), and 2) To characterize longitudinal
CMV-specific humoral (nAb) and cellular (T-cell, NK cell) immune responses and their association with
prevention strategy, CMV infection (DNAemia) in the PET arm, and Endpoint Committee confirmed CMV
disease. The Aims will be accomplished with a 5-center trial of 360 adult CMV D+R- KTR who will be
randomized 1:1 to a standardized PET protocol for 100d (described above) or to AP (200d of VALGAN or
letermovir). CMV-specific immunity assessments at 3, 6, 12, 24, and 36 months will include nAb, NK cells, and
multifunctional T-cells with multi-color flow cytometry that incorp...

## Key facts

- **NIH application ID:** 11247853
- **Project number:** 7R01AI184205-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Daniel Conlon Brennan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,254,477
- **Award type:** 7
- **Project period:** 2024-07-12 → 2031-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11247853

## Citation

> US National Institutes of Health, RePORTER application 11247853, Kidney transplant Preemptive therapy or Prophylaxis (KPoP) for CMVPreventionin D+R- Recipients (7R01AI184205-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11247853. Licensed CC0.

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