HAART-Induced Reconstitution of Herpes Simplex Virus-specific IFN-γ CD4 T Cell Response Is Highly Correlated to CD4 Cell Count Gain

Abstract

M Ramaswamy1, A Waters1,2, E Hainsworth1, C Smith1, G Hardy1, M Johnson1, JAinsworth2, A Phillips1, and Anna Maria GerettiAuthor Email1 1Royal Free and Univ Coll Med Sch, London, UK and 2North Middlesex Hosp, London,UK Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 786 February 5, 2006 BACKGROUND: Secretion of interferon-gamma (IFN-γ) by activated T cells has beenproposed as a key protective mechanism against herpes simplex virus (HSV) infection.We reported previously that the clinical expression of HSV infection declined in HIV-infected patients after the introduction of HAART, suggesting restoration ofimmunologic control. Our aim here was to study HSV-specific T-cell immunity inperipheral blood of HIV-infected persons at different disease stages.METHODS: We investigated 4 HIV-infected groups: A) long-term slow/non-progressors(LTSP/LTNP) with CD4 >450 cells/mm3 over ≥10 years, sampled at 3 time points; B)newly diagnosed patients; C) patients stable on HAART; D) patients starting HAARTsampled prospectively. Control groups: HSV IgG seropositive (HSV+) andseronegative (HSV-) healthy donors sampled at 3 time points and HSV- HIV-infectedpersons with CD4 >250. IFN-γ production of fresh peripheral blood mononuclear cells(PBMC) (triplicate wells) stimulated with HSV-1 and HSV-2 lysates (1, 5, and 10µg/mL) were assayed by ELISpot. The mean number of spot-forming cells (SFCn) per106 PBMC was determined by an automated reader. Responses were furthercharacterised by intracellular cytokine staining (ICS).RESULTS: SFCn was 320±90 in HSV+ healthy donors (n = 11) and 28±11 in HSV-donors (n = 9); responses were stable over 9 weeks. SFCn was 30±18 in HSV- HIV-infected persons (n = 10, median CD4 457). SFCn of HSV+ HIV-infected persons was:A) LTSP/LTNP (n = 3, median CD4 953): 334±82, stable over ≤43 weeks. B) newlydiagnosed patients (n = 9, median CD4 453): 186±51. C) patients on stable HAART (n= 33, median CD4 360, 91% with viral load <400 copies/mL): 181±59. D) 9 patients