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O17.5 Increased herpes simplex virus-2 shedding in hiv-1 infected persons is due to poor immunologic control in both ganglia and genital mucosa
  1. JT Schiffer1,2,3,
  2. DA Swan1,
  3. A Magaret1,4,5,
  4. A Wald1,3,4,6
  1. 1Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  2. 2Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  3. 3Department of Medicine, University of Washington, Seattle, Washington, USA
  4. 4Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
  5. 5Department of Biostatistics, University of Washington, Seattle, Washington, USA
  6. 6Department of Epidemiology, University of Washington, Seattle, Washington, USA

Abstract

Introduction A signature feature of HIV infection is poor control of herpesvirus infections, which reactivate from latency and lead to opportunistic infections. While the general mechanism underlying this observation is deficient CD4+T-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether CD4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic responses.

Methods Here we compare genital shedding patterns of herpes simplex virus-2 (HSV-2) in 98 HIV infected and 98 HIV uninfected men matched on length of infection, HSV-1 serostatus and nationality.

Results We demonstrate that high copy HSV-2 shedding is more frequent in HIV positive men, particularly in participants with CD4+ T-cell count <200/μL. Genital shedding is more frequent due to higher rate of shedding episodes, as well as a higher proportion of prolonged shedding episodes. Peak episode viral load was not found to differ between HIV infected and uninfected participants regardless of CD4+ T-cell count. We simulated a mathematical model which recapitulated these findings and identified that rate of HSV-2 release from neural tissue increases, duration of mucosal cytolytic immune protection decreases, and cell-free viral lifespan increases in HIV infected participants.

Conclusion These results suggest that increased HSV-2 shedding is due to impaired immune function in both latent and lytic tissue compartments, with deficits in both humoral and cell-mediated HSV-2 clearance.

Disclosure of interest statement No commercial contributions were received that are relevant to this work.

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