Reconstitution of HSV-specific T-cell immunity in HIV-1 infected patients receiving highly active antiretroviral therapy (HAART)

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Reconstitution of HSV-specific T-cell immunity in HIV-1 infected patients receiving highly active antiretroviral therapy (HAART)

Presenter: Meghna Ramaswamy. Department of Virology, Royal Free and University College Medical School, London, UK.

Background: Interferon (IFN)-g producing CD4 cells are key mediators of protective immunity against herpes simplex virus (HSV). This study measured HSV-specific IFN-g production by peripheral blood mononuclear cells (PBMC) of HIV-1-infected persons at different disease stages and the kinetics of highly active antiretroviral therapy (HAART)-induced reconstitution of HSV-specific T-cell responses.

Methods: PBMC stimulated with HSV lysates were assayed by ELISPOT. Responses were further characterized by intracellular cytokine staining.

Results: In 11 HSV IgG-seropositive healthy donors, the mean number of spotforming cells/106 PBMC (SFC) was 314ą74, stable over 9 weeks. Among HSV IgGseropositive HIV-1 infected persons, SFC were 360ą69 in three long-term non-progressors (LTNP), (median CD4 1219 cells/mm3); 186ą52 in nine newly diagnosed patients (CD4 453 cells/mm3); and 181ą59 in 33 patients receiving HAART for median 30 (1109) months (CD4 360 cells/mm3). Nine patients started first-line HAART; all achieved HIV-1 RNA <50 copies/mL. Over median 40 (2664) weeks SFC increased by 5.6/month (95% CI: +1.2, +9.9; P=0.01). SFC were correlated with LTNP status and CD4 count, and increased by +21.3 (95% CI: +13.8, +28.7; P<0.0001) per 100 CD4 cells/mm3 gained.

Conclusions: Successful HAART resulted in slow restoration of HSV-specific immunity. Responses were not directly predicted by duration of HAART, but were strongly correlated with CD4 count recovery.


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