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Transpl Int. 2018 Jun;31(6):639-648. doi: 10.1111/tri.13142. Epub 2018 Mar 13.

Delay of alternative antiviral therapy and poor outcomes of acyclovir-resistant herpes simplex virus infections in recipients of allogeneic stem cell transplant - a retrospective study.

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Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
McGovern Medical School, The University of Texas Science Center at Houston, Houston, TX, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.


Acyclovir is commonly used to prevent and treat herpes simplex virus (HSV) reactivation after hematopoietic cell transplant (HCT), and only few reports have been published on acyclovir-resistant HSV in HCT recipients. We reviewed the medical records of patients with a microbiologic diagnosis of acyclovir-resistant HSV by plaque reduction test who received an HCT from 2002 through 2014. A total of 4 028 HCTs were performed during the study period, and 18 of the recipients met the diagnostic criteria for acyclovir-resistant HSV. All cases had undergone allogeneic HCTs. Most patients were in the pre-engraftment period or on systemic corticosteroid therapy for graft-versus-host disease (GVHD). The median time between diagnosis and susceptibility testing was 15 days, and antiviral therapy was changed at a median of 27 days. Patients required prolonged therapy (~80 days), and many had serious complications including renal failure and hospitalization. In conclusion, acyclovir-resistant HSV infection is more likely during the period of profound deficit in T-cell-mediated immunity and is associated with significant morbidities. Higher doses of acyclovir prophylaxis might be needed for patients with history of HSV during pre-engraftment or GVHD treatment. In patients who do not respond or progress after 1 week of acyclovir therapy, testing for drug-resistant HSV, and early switch to an alternative antiviral should be considered.


acyclovir resistance; herpes simplex virus infection; stem cell transplant

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