Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation

Abstract

The negative impact of cytomegalovirus (CMV) infection on transplant outcomes warrants efforts toward improving its prevention, diagnosis, and treatment. During the last 2 decades, significant breakthroughs in diagnostic virology have facilitated remarkable improvements in CMV disease management. During this period, CMV nucleic acid amplification testing (NAT) evolved to become one of the most commonly performed tests in clinical virology laboratories. NAT provides a means for rapid and sensitive diagnosis of CMV infection in transplant recipients. Viral quantification also introduced several principles of CMV disease management. Specifically, viral load has been utilized (i) for prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and (v) to indicate the risk of clinical relapse or antiviral drug resistance. However, there remain important limitations that require further optimization, including the interassay variability in viral load reporting, which has limited the generation of standardized viral load thresholds for various clinical indications. The recent introduction of an international reference standard should advance the major goal of uniform viral load reporting and interpretation. However, it has also become apparent that other aspects of NAT should be standardized, including sample selection, nucleic acid extraction, amplification, detection, and calibration, among others. This review article synthesizes the vast amount of information on CMV NAT and provides a timely review of the clinical utility of viral load testing in the management of CMV in solid organ transplant recipients. Current limitations are highlighted, and avenues for further research are suggested to optimize the clinical application of NAT in the management of CMV after transplantation.

Fig 1

Strategies for prevention of cytomegalovirus disease in transplant recipients. (A) Antiviral prophylaxis. An antiviral drug, most commonly valganciclovir, is given to all at-risk patients for a defined period after transplantation. In general, the duration is 3 to 6 months, although it can be shortened (backward arrow) or prolonged (forward arrow) depending on the risk profile. (B) Preemptive therapy. This strategy entails routine cytomegalovirus surveillance by nucleic acid testing (often on a weekly basis, as indicated by arrows). Upon detection of a positive viral load threshold, antiviral treatment is initiated and continued until the viral level falls below the clinically relevant threshold. Viral load monitoring for patients is usually conducted during the first 3 months after transplantation. (C) Hybrid approach, wherein antiviral prophylaxis is followed by a preemptive strategy. This is an approach to reduce the incidence of late-onset cytomegalovirus disease in high-risk transplant patients who start off with antiviral prophylaxis as the primary method of cytomegalovirus prevention.