Background: It is unknown whether a Toxoplasma gondii-specific T cell response is restored after successful combined antiretroviral therapy (cART) in patients with AIDS and current or previous toxoplasmic encephalitis (TE). Methods: We performed a multicenter cross-sectional study with 17 healthy T. gondii-positive human immunodeficiency virus (HIV)-1-uninfected individuals and 90 patients coinfected with HIV-1 and T. gondii distributed in 5 groups according to their CD4+ T cell counts and T. gondii infection (with or without current or previous TE). We investigated the lymphocyte proliferative response (LPR) and interferon (IFN)-γ production in response to T. gondii soluble antigen extract (SATg) and as CD4+ and CD8+ T cell subsets. Results: SATg-specific LPR and IFN-γ production were not observed in many of the most immunosuppressed patients (CD4+ T cell count, 200 cells/μL) who presented with TE and had already stopped secondary TE prophylaxis. Similar results were found in immunocompetent asymptomatic patients who did not receive TE prophylaxis. The predictors of SATgspecific T cell responses and IFN-γ production were a cART-mediated increase in CD4+ T cell count and LPR to phytohemagglutinin and viral suppression and a decrease in the activated (CD38+) CD8+ T cell count, respectively. Conclusions: cART restores T. gondii-specific CD4 T cell responses in most patients with AIDS who had previous TE. Our data support the safety of withdrawing TE prophylaxis when the CD4+ T cell count returns to levels >200 cells/μL. © The Author 2011. ; SCOPUS: ar.j ; info:eu-repo/semantics/published