What is the role of ganciclovir in prophylaxis against cytomegalovirus (CMV) disease?

Updated: Jul 07, 2021
  • Author: Ricardo Cedeno-Mendoza, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Answer

A major successful use of ganciclovir has been prophylactic or preemptive treatment of CMV disease in transplant recipients. Without preventive CMV therapy, 30%-75% of transplant recipients develop CMV infection, and 8%-30% develop CMV disease. [68, 69]

Oral ganciclovir has been replaced by valganciclovir for prophylaxis and preemptive therapy because of bioavailability issues.

Prophylaxis is provided to all patients who have positive CMV serology results. Positive findings on blood cultures, pp65 antigenemia, and CMV PCR have been used as markers for the initiation of therapy. Both the prophylactic and the preemptive approaches have been used, and both have been found to decrease CMV disease in bone marrow or solid organ transplants recipients. The choice of the appropriate regimen may be determined by the adverse effects of the drugs and the abilities of the microbiology laboratory. Universal prophylaxis versus preemptive therapy as the best approach remains a matter of debate and varies among institutions. Recent data favor universal prophylaxis with either ganciclovir or valganciclovir in high-risk liver transplant recipients. [70]

Preemptive therapy is attractive because it restricts the use of ganciclovir to a select population at high risk for CMV disease, eliminates toxicity in most patients who would not be diagnosed with CMV disease, and decreases the cost of medical care.

A study compared 96 renal transplant recipients in Italy between May 2006 and December 2007, all of whom received preemptive therapy with ganciclovir and/or valganciclovir, with 100 controls who received CMV prophylaxis. Serial quantitative viral loads were obtained weekly during the first 4 months. Asymptomatic patients, with a viral load DNA of more than 100,000 copies/mL determined using PCR, were treated with for 3 months or until resolution of viral replication. Among the 96 transplant recipients, blood CMV viral loads were elevated in 14 asymptomatic patients, who were treated with oral valganciclovir for 3 months. After a median follow-up period of 13.3 months, none of the 14 patients who received valganciclovir developed CMV disease, leading the authors to conclude that valganciclovir administered as preemptive therapy was safe and efficacious in preventing CMV disease. [71]

Conversely, a study using CMV pp65 antigenemia as the trigger for treatment found prophylaxis to be more effective than preemptive therapy for preventing CMV pneumonia in marrow transplant recipients. [72] At the same time, however, ganciclovir at engraftment was associated with more early invasive fungal infections and more late CMV disease. [72]

Some experts believe CMV prophylaxis in solid organ transplant recipients may protect against indirect CMV effects not measurable by levels, such as graft rejection, opportunistic infections, and transplant-associated vasculopathy. [68]

Prophylactic approaches have also been very successful in eliminating CMV disease; however, toxicities are increased with this approach because patients without viral reactivation may be exposed to antiviral therapy. Many transplantation centers reserve prophylactic therapy for patients most at risk (CMV-positive donors/CMV-negative recipients) for disease reactivation and use antigen assays to institute preemptive therapy in other patients.

Some experts recommend extending the duration of CMV prophylaxis to the period of reduced immunosuppression. They feel this may protect patients from late-onset CMV disease. [68]

Prolonged ganciclovir use has been associated with development of resistance.


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