796 Timing of reconstitution of Toxoplasma gondii-specific T-cell Responses in AIDS Patients with Acute Toxoplasmic Encephalitis After Starting HAART: A Prospective Multi-center Longitudinal Study J. M. Miro*1, M. Lejeune1, X. Claramonte1, E. Martinez1, E. Ribera2, J. Arrizabalaga3, J. R. Arribas4, P. Domingo5, D. Podzamczer6, M. Crespo2, M. Plana1, M. E. Valls1, F. Garcia1, A. Jacquet7, J. M. Gatell1, O. Sued1, E. Lazzari1, J. L. Blanco1, T. Gallart1 1Hosp Clin, IDIBAPS, Barcelona, Spain; 2Hosp V Hebrón, Barcelona, Spain; 3Hosp Ntra Sra De Aranzazu, San Sebastian, Spain; 4Hosp La Paz, Madrid, Spain; 5Hosp St Pau, Barcelona, Spain; 6Hosp de Bellvitge, Barcelona, Spain; and 7Univ Libre de Bruxelles, Belgium
Background: There are few data about the timing of the reconstitution of the Toxoplasma gondii(Tg)-specific T-cell immune responses in AIDS patients (pts) with acute Toxoplasmic Encephalitis (TE) after starting HAART.
Methods: Prospective multicenter longitudinal study that enrolled AIDS patients (pts) with acute TE. T-cell subsets, plasma RNA HIV-1 viral load (PVL), Th1 and Th2 cytokine production, and PBMC lymphoproliferative responses (LPR) to soluble antigen extract of Tg (SATg) were performed at baseline (T0) and thereafter at 3 (T3), 6 (T6), 9-12 (T12), and 15-18 (T18) months (mos) after starting HAART. All pts were receiving TE maintenance therapy. A stimulation index (SI) > 10 was the cutoff used for a positive LPR response. The production of IFN-gamma in the supernatant from SATg-stimulated cultures at 72 hrs was also determined.
Results: Twenty-six (26) pts were included in the study. Six (6) pts were not eligible (2 early deaths, 2 cases were lost for follow-up, and 2 cases did not have TE). All pts had IgG antibodies against Tg (median [IQR] titer of 208 [131-300] UI/mL). Sixteen (16) pts were sampled at 3 mos (T3), 8 cases at 6 mos (T6), 13 pts at 9-12 mos (T12), and 6 cases at 16-18 mos (T18). Median (IQR) CD4+ T-cell count at T0, T3, T6, T12, and T18 was 5 (3-35), 143 (43-346), 296 (166-455), 195 (76-394), and 301 (191-369) cells/µL, respectively. At the same time points, the proportion of cases with plasma HIV VL < 200 copies/mL was 0%, 30%, 50%, 90%, and 83%, respectively; the median (IQR) LPR was 1.24 (0.8-5), 5.39 (2.5-9), 5.79 (1.7-12.7), 9.53 (2.2-12.5) and 20.3 (9.9-39), respectively; a positive LPR (SI > 10) was detected in 10%, 19%, 25%, 46%, and 83%, respectively; the median (IQR) INF-gamma production in response to SATg was 0 (0-1), 0 (0-74), 0 (0-27), 0 (0-344) and 69 (22-838) pg/mL, respectively. The restoration of a positive LPR to SATg was negatively correlated with the plasma HIV VL and positively correlated with the CD4+ T-cell count (p < 0.001).
Conclusions: After 15-18 mos of HAART, T-cell responses to SATg were restored in most pts who had an acute TE episode. This data may help us to know better when to stop TE maintenance therapy in pts with HAART.
