Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Rev Med Virol. 2019 Mar;29(2):e2023. doi: 10.1002/rmv.2023. Epub 2018 Dec 17.

Abstract

Human cytomegalovirus (CMV) represents the most common infection among recipients of solid organ transplants (SOTs). Previous meta-analysis showed 0.8% of SOT recipients developed CMV disease whilst receiving valganciclovir (ValGCV) prophylaxis. However, the clinical utility of monitoring ganciclovir (GCV) blood concentrations is unclear. We systematically reviewed the association between GCV concentrations during prophylaxis and the incidence of CMV. MEDLINE and EMBASE databases were searched for studies between 1946 and 2018, where GCV pharmacokinetics and incidence of CMV viraemia or disease in SOT were available. Research designs included randomised trials, comparative, prospective cohort, retrospective, or case report studies. Only human adult studies were included, with English language restriction. The 11 studies that met the eligibility criteria included 610 participants receiving GCV or ValGCV prophylaxis. Quality assessment showed 2/4 randomised trials, 4/6 cohort studies, and 1/1 case report were of high quality. Despite dose adjustments for renal impairment, mean GCV exposures for patients were heterogeneous and ranged between 28 and 53.7 μg·h/mL across three randomised trials. The incidence of CMV infection and disease ranged from 0% to 50% and 0% to 3.1%, respectively, with follow up between 3 to 9 months. One study showed statistical power in determining relationship, where GCV exposure at 40 to 50 μg·h/mL in high-risk SOT recipients was associated with a reduced risk of viraemia. Clinical monitoring for GCV exposure can be applied to high-risk SOT recipients during ValGCV prophylaxis; however, further studies are needed to determine the utility of monitoring in all SOT recipients.

Keywords: cytomegalovirus; ganciclovir; solid organ transplant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / pharmacology*
  • Base Composition
  • Chemoprevention / methods
  • Cytomegalovirus Infections / epidemiology
  • Cytomegalovirus Infections / prevention & control*
  • Female
  • Ganciclovir / administration & dosage
  • Ganciclovir / pharmacokinetics*
  • Ganciclovir / pharmacology*
  • Humans
  • Immunocompromised Host*
  • Incidence
  • Male
  • Middle Aged
  • Organ Transplantation*
  • Prospective Studies
  • Retrospective Studies
  • Transplant Recipients
  • Treatment Outcome
  • Viremia / epidemiology
  • Viremia / prevention & control
  • Young Adult

Substances

  • Antiviral Agents
  • Ganciclovir