Resistance to antiviral drugs in herpes simplex virus infections among allogeneic stem cell transplant recipients: Risk factors and prognostic significance

Herpes simplex virus (HSV) infections in 75 allogeneic stem cell transplant recipients were analyzed. Sixteen patients developed HSV disease following transplantation. The risk factors were age, sex (females), unrelated donor graft, and graft-versus-host disease (GVHD) grade greater than or equal to 2. Seven patients did not respond to acyclovir, and 3 patients failed to respond to foscarnet, Isolates from 4 patients developed resistance to acyclovir/penciclovir, and 3 patients had foscarnet-resist ant isolates. The remaining 3 patients failed to respond to acyclovir, despite having sensitive isolates. All the isolates were sensitive to cidofovir, for which the IC50 values correlated inversely with those for acyclovir (P = .01). The risk factors for clinical resistance to antiviral drugs were a GVHD grade greater than or equal to 2 (P = .001) and the lack of ganciclovir prophylaxis (P = .01), with a higher nonrelapse mortality in the latter group (P < .0001). Clinical as well as in vitro resistance to antiviral drugs is common in patients with severe GVHD and is associated with a poor outcome.