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S09.3 Herpes Simplex Virus
  1. E Frobert1,2,
  2. S Ducastelle-Lepretre3,
  3. J Casalegno1,2,
  4. V Nave1,
  5. D Eibach4,1,
  6. B Lina1,2,
  7. F Morfin1,2
  1. 1Laboratory of Virology, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Lyon, France
  2. 2Virologie et Pathologie Humaine, Université Lyon 1, EA 4610, Faculté de Médecine RTH Laënnec, Lyon, France
  3. 3Service d’hématologie Clinique, Centre Hospitalier Lyon Sud, Lyon, France
  4. 4European Public Health Microbiology Training Programme (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden

Abstract

The more and more frequent and widespread use of acyclovir (ACV), but also the increasing number of immunocompromised patients might induce an increase in HSV (Herpes Simplex Virus) resistance. HSV resistance to ACV is mainly associated with mutations in the thymidine kinase (TK) gene although mutations in the DNA polymerase can be observed. Up to now, resistance of HSV to ACV was a major concern for immunocompromised patients with a frequency between 2.5 and 10%. This study aimed to reassess HSV resistance to ACV, during a ten year period, in immunocompetent and in immunocompromised patients (bone marrow transplant patients, solid organ transplant, HIV positive patients, cancer patients). From 2002 to 2011, 1538 patients positive for HSV were tested for the susceptibility of their virus to ACV (1044 immunocompetent and 494 immunocompromised). In immunocompetent patients, prevalence of resistance remains under 0.5%, whatever the period studies. In immunocompromised patients, a significant increase can be observed, from 4.3% during 2002–2006 (11/255 patients) to 13.4% during 2007–2011 (32/239) (p = 0.0002). This significant increase is mainly observed among bone marrow transplant patients in which the prevalence is 10% (5/52) during 2002–2006 and 38% (30/79) during 2007–2011 (p = 0.0002), whereas other types of immune deficiencies do not show an increase (1.3% versus 2.9%, p = 0.2). New chemotherapy protocols (FLAMSA) and type of transplantation as blood cord transplant are part of the explanation. Genotyping of the resistant viruses (35 viruses) reveal mutations in the TK gene for 80% of them. Double population including resistant and susceptible viruses were recovered in 5 isolates (5/34 = 14%). Rapid diagnosis of HSV resistance, but also research on alternative treatment are more than ever of interest.

  • acyclovir
  • herpes simplex virus
  • Resistance

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