CMV antiviral stewardship: navigating obstacles to facilitate target attainment

Abstract

Purpose of review Despite the availability of potent antivirals, consensus guidelines and decades of research, cytomegalovirus (CMV) continues to be associated with negative outcomes after solid organ transplant. This has been attributed to postprophylaxis CMV infection and a lack of development of CMV-specific cell mediated immunity (CMI). A shift from a focus on antiviral prevention to a focus on CMI target attainment is needed to improve CMV outcomes after transplantation. Recent findings There are many obstacles to CMI target attainment. Antiviral stewardship programs (AVS) have been employed to improve patient outcomes through appropriate antiviral use, reduction of unnecessary exposure and resistance mitigation. By focusing on the patient's unique substrate of conglomerate risk factors and addressing these factors specifically with evidenced based methodology, the AVS can address these obstacles, increasing rates of CMI and subsequently reducing risk of future CMV infection and negative outcomes. Summary With its multidisciplinary composition utilizing decades of experience from antimicrobial stewardship principles and practices, the AVS is uniquely poised to facilitate the shift from a focus on prevention to CMI target attainment and be the supporting pillar for the frontline transplant clinician caring for transplant patients with CMV.

Impact of an ultrasensitive Cytomegalovirus quantitative nucleic acid test on Cytomegalovirus detection and therapy in renal transplant recipients

“…This suggests that careful monitoring without immediate antiviral treatment could be feasible for patients with low‐level CMV DNAemia. Furthermore, antiviral stewardship programs have advocated for preemptive therapy in CMV prevention and the use of CMV cell‐mediated immune assays to guide duration of surveillance monitoring 16,17 . Preemptive therapy in liver transplant recipients was shown to enable immune system priming, leading to the development of neutralizing antibodies and reducing the risk of delayed‐onset post‐prophylaxis CMV disease, compared to those on antiviral prophylaxis 18 .…”

“…Furthermore, antiviral stewardship programs have advocated for preemptive therapy in CMV prevention and the use of CMV cell-mediated immune assays to guide duration of surveillance monitoring. 16,17 Preemptive therapy in liver transplant recipients was shown to enable immune system priming, leading to the development of neutralizing antibodies and reducing the risk of delayed-onset post-prophylaxis CMV disease, compared to those on antiviral prophylaxis. 18 These findings, coupled with our own, suggest that controlled exposure to low-level CMV DNAemia could potentially enhance CMV-specific immunity and antiviral stewardship, without compromising patient outcomes.…”

The next frontier: cytomegalovirus antiviral stewardship programs in solid organ transplant

“…Letermovir has utility as a prophylaxis agent that lacks the myelosuppressive adverse effects of (val)ganciclovir that can require varying degrees of medical management [15]; additionally, letermovir may promote an environment conducive to the development of CMV-specific CMI and long-term control of viral replication independent of antiviral therapy [32]. This effect of letermovir, along with CMV ASP-led initiative preemptive monitoring and resulting immune priming with viral replication, may be especially valuable as programs shift their focus to a new goal: development of CMV-specific CMI [33].…”

What’s New: Updates on Cytomegalovirus in Solid Organ Transplantation

“…Development of CMV-specific CMI posttransplantation is critical to improving CMV-specific outcomes and reducing need for prolonged antivirals, which is a major contributor to CMV resistance. 128 Cell-mediated immunity target attainment is a critical element to a CMV stewardship program. A pharmacist-driven CMV stewardship program in ambulatory SOT recipients implemented at large medical center showed fewer patients reaching CMV viral load of >10 000 IU/mL before treatment, and a greater proportion of patients achieving viral clearance at 21 d. 129 Of note, there were numerically fewer episodes of CMV resistance at 1 y.…”