Predictors for Cytomegalovirus Resistance in Kidney Transplant Recipients

Prolonged valgancilovir in CMV-positive KTRs was associated with antiviral drug resistance, suggesting the need for alternative strategies to achieve CMV viral clearance in this population.

Among kidney transplant recipients (KTRs) who are positive for cytomegalovirus (CMV), prolonged exposure to valganciclovir (VGCV) for 8 or more weeks during CMV replication may be associated with antiviral drug resistance. These study findings were published in Open Forum Infectious Diseases.

Researchers conducted a single-center retrospective study among KTR recipients (N=313) who received treatment for CMV infection between 2004 and 2017. Viral resistance in CMV was evaluated on the basis of CMV treatment strategy and duration. The researchers defined CMV infection as CMV DNAemia of at least 1000 IU/mL without symptoms; CMV disease as symptomatic CMV infection; early-onset CMV infection as onset within 3 months of transplantation; and late-onset CMV as onset at more than 3 months after transplantation.

Among 313 patients included in the analysis, the median age was 57 (IQR, 48-65) years, 65% were men, 84% received dialysis prior to transplantation, and the median estimated glomerular filtration rate at CMV onset was 40 (IQR, 30-55) mL/min/1.73 m2.

The donor and recipient CMV serostatuses were positive and negative (45.7%), positive and positive (34.2%), negative and positive (15%), and negative and negative (1.3%), respectively. After transplantation, 47.3% of patients received universal prophylaxis and 47.3% received preemptive CMV treatment; the preventive strategy used among the remaining patients (5.4%) was unknown.

At onset, 69.6% of patients were diagnosed with CMV disease and 30.4% with CMV infection. The median time from transplantation to CMV onset was 137 (IQR, 45-249) days. The initial treatment strategy was intravenous ganciclovir for 52.7% of patients and oral VGCV for 47.3%.

Antiviral drug resistance was noted in 20 patients, occurring at a median of 112 days after treatment initiation. At CMV diagnosis, the median CMV DNAemia was 39,600 IU/mL. No significant differences were observed between KTRs who did vs did not develop antiviral drug resistance in regard to graft survival at 2 years (hazard ratio [HR], 2.85; 95% CI, 0.68-11.88; P =.14).

The question as to whether antiviral drug resistance is the cause or the consequence of persisting CMV DNAemia requiring treatment with (V)GVC for more than 8 weeks remains unanswered.

Significant independent predictors for CMV resistance included the need for 8 or more weeks of VGCV treatment due to persistent DNAemia (adjusted HR, 11.68; 95% CI, 2.62-52.01; P =.001) and low lymphocyte count at day 49 (aHR, 0.22; 95% CI, 0.05-0.92; P =.04).

Predictors for requiring VGCV treatment beyond 8 weeks included CMV seropositivity in the donor and seronegativity in the KTR (aHR, 5.56; 95% CI, 2.44-14.29; P <.001), the use of VGCV prophylaxis vs preemptive treatment (aHR, 0.20; 95% CI, 0.08-0.48; P <.001), and low lymphocyte count at day 49 (aHR, 0.20; 95% CI, 0.07-0.54; P =.002).

Study limitations include the retrospective design and substantial changes that occurred during the study period in regard to the clinical management of KTRs.

According to the researchers, “The question as to whether antiviral drug resistance is the cause or the consequence of persisting CMV DNAemia requiring treatment with (V)GVC for more than 8 weeks remains unanswered.”


Acquier M, Taton B, Alain S, et al. Cytomegalovirus DNAemia requiring (val)ganciclovir treatment for more than 8 weeks is a key factor in the development of antiviral drug resistance. Open Forum Infect Dis. Published online January 23, 2023. doi:10.1093/ofid/ofad018