Restoration of Toxoplasma gondii-specific immune responses in patients with AIDS starting HAART.
OBJECTIVE
To study the kinetics and identify factors associated with Toxoplasma-specific immune responses in patients with AIDS starting antiretroviral therapy.


METHODS
A prospective study of 38 HIV-infected patients seropositive for Toxoplasma who started antiretroviral therapy with CD4 T cells less than 200 cells/microl. T-cell and B-cell phenotypes, anti-Toxoplasma antibodies titers, Th-1 and Th-2 cytokine production and lymphocyte proliferative responses (LPRs) to Toxoplasma were assessed over 12 months.


RESULTS
Median CD4 cell count increased from 122 cells/microl at baseline to 260 cells/microl at 12 months, and the incidence of a positive LPR from 18.4 to 70.5%. A Toxoplasma IgG titer more than 150 IU/ml was the only baseline variable associated with a positive LPR (hazard ratio: 4.6, P = 0.003). Among time-dependent covariates, the number of effector memory (CD45RA-CCR7-) CD4 T cells was associated with a positive LPR (P < 0.02) and the number of terminally differentiated (CD45RA+CCR7-) CD8 T cells was associated with in-vitro production of gamma-IFN (P < 0.008).


CONCLUSIONS
Among patients with low CD4 cell counts, high anti-Toxoplasma IgG titers were associated with LPR to Toxoplasma antigen. After starting antiretroviral therapy, the number of effector memory CD4 T cells and terminally differentiated CD8 T cells were associated with the restoration of Toxoplasma LPR and gamma-IFN production, respectively.
Furco
André
A
Department of Infectious Diseases, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris and University of Paris 7, Paris Diderot, Paris, France.
Carmagnat
Maryvonnick
M
Chevret
Sylvie
S
Garin
Yves J-F
YJ
Pavie
Juliette
J
De Castro
Nathalie
N
Charron
Dominique
D
Derouin
Francis
F
Rabian
Claire
C
Molina
Jean-Michel
JM
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D000328:Adult; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*
D019380:Anti-HIV Agents; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D007371:Interferon-gamma