Recalcitrant pseudotumoral anogenital herpes simplex virus type 2 in HIV-infected patients: evidence for predominant B-lymphoplasmocytic infiltration and immunomodulators as effective therapeutic strategy

Clin Infect Dis. 2013 Dec;57(11):1648-55. doi: 10.1093/cid/cit592. Epub 2013 Sep 24.

Abstract

Background: In patients with human immunodeficiency virus (HIV) infection, genital herpetic lesions may be extensive and tend to persist for longer periods; in addition, atypical hypertrophic, ulcerative, or pseudotumor forms have been reported, frequently showing resistance to acyclovir (ACV) treatment.

Methods: Between 2003 and 2011, 10 HIV-1-infected patients presenting with chronic pseudotumoral anogenital herpes simplex type 2 (HSV-2) infections were studied.

Results: All patients developed chronic, hypertrophic HSV-2 anogenital lesions with multilesional presentation in 7 cases and involvement of 2 anatomical sites in 6 of them. At the time of diagnosis, the median CD3(+)CD4(+) absolute blood count was 480.5 cells/µL (range, 165-632 cells/µL), whereas the plasma HIV load was undetectable in all cases. Histopathologic analysis of lesion biopsies showed a moderately dense dermal polytypic plasma cell infiltrate. Detection of HSV-2 by culture and/or polymerase chain reaction was positive for all patients, with evidence for ACV-resistant strains in 6 of 8 cases. In addition, viral resistance to ACV was found only in HSV-2 isolated from ulcerative lesions, whereas purely pseudotumoral ones harbored sensitive strains. Durable control was observed with HSV DNA polymerase inhibitors in only 2 cases, and the immunomodulators imiquimod and thalidomide allowed 5 patients to reach sustained complete response.

Conclusions: HSV-2-related pseudolymphoma in HIV-infected patients is characterized by a predominant polyclonal lymphoplasmacytic infiltration, and is frequently refractory to antiherpetic drugs. Immunomodulatory therapeutic strategies using thalidomide showed consistent efficacy, and should be considered early during the course of disease.

Keywords: AIDS; HIV; acyclovir-resistant HSV infection; human immunodeficiency virus; pseudotumoral anogenital herpes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / therapeutic use
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Drug Resistance, Viral
  • Female
  • HIV Infections / virology*
  • Herpes Genitalis / pathology
  • Herpes Genitalis / therapy*
  • Herpes Genitalis / virology*
  • Herpesvirus 2, Human / drug effects
  • Herpesvirus 2, Human / isolation & purification*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Mutation
  • Thalidomide / therapeutic use
  • Thymidine Kinase / genetics

Substances

  • Antiviral Agents
  • Immunosuppressive Agents
  • Thalidomide
  • Thymidine Kinase
  • Acyclovir