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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