Combination antiviral CMV therapy with ganciclovir and foscarnet in high risk infants

Background: Newborn screening for immune deficiencies including severe combined immunodeficiency is being implemented nationwide, knowing that hematopoietic stem cell transplantation dramatically improves survival. A major risk factor in these infants is CMV infection, which decreases transplant success. Specific antiviral therapy must be early and aggressive because of the potential for resistance and rapid dissemination. Combination antiviral therapy is routine for some viral infections such as HIV, but the value of this approach for CMV is unclear.

Methods: Medical records of infants ≤ 6 months (M) of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or combination GCV + FOS for CMV disease, with viral loads followed, were studied. Patients receiving prophylaxis only were excluded. Viral load data, absolute neutrophil and platelet counts, serum creatinine, electrolytes, and results of CMV resistance testing, if performed, were reviewed.

Results: Four children (mean, 2.5 M; range, 2-3.4 M) received initial combination GCV + FOS while 25 children (mean age 2.8 M; range,1.3-6.0 M) received either GCV or FOS monotherapy. Median initial and peak viral loads were higher in the combination therapy group and these patients all demonstrated initial improvement in viral loads. Three of four recovered. Toxicity was common in both groups; neutropenia, thrombocytopenia and electrolyte abnormalities occurred most frequently. Resistance testing was not routinely performed in children receiving monotherapy, but 3 of 4 infants in the GCV+FOS group did have testing; no mutations were detected.

Conclusion: Combination GCV + FOS therapy may be an effective alternative to monotherapy with GCV or FOS alone in high-risk infants, especially in those with primary immune deficiencies. Although our findings are limited by small numbers at a single center, toxicity from mono- and combination therapy was comparable. Despite protracted infections and high viral loads in high-risk infants receiving GCV+FOS, CMV resistance was not detected. Although the numbers treated with combination therapy is too small to assess the impact on the development of resistance or overall survival, this approach should be studied further.