Background: An elevated IgE level and increased production of T H2 cytokines are factors associated with poor prognosis in HIV infection. We report a pediatric long-term survivor of vertically acquired HIV infection with a normal CD4 count and a low viral burden despite the lack of antiretroviral therapy and a phenotype resembling hyper-IgE syndrome. Objective: We sought to characterize the patient’s T H1 versus T H2 cytokine profile and anti-HIV–specific immune responses. Methods: Supernatants collected from cultures of peripheral blood T cells stimulated with phorbol myristate acetate plus ionomycin were assayed for T H1 and T H2 cytokines by means of ELISA. Specific IgE antibodies were determined by immunoblot. HIV-specific cytotoxic T-lymphocyte responses were measured from cell lysis by fresh T cells of autologous B-lymphoblastoid cells expressing recombinant HIV proteins. Results: Patient CD4 + T cells secreted significantly more T H2 cytokines, IL-4 ( P < .003) and IL-5 ( P < .03), than HIV-infected and seronegative control cells. No difference was noted in T H1 cytokine production. IgE specific for HIV gp160, p24, p17, and p66 proteins and Aspergillus fumigatus was detected in patient sera. Despite predominance of T H2 cytokines, HIV-specific cytotoxic T-lymphocyte activity was vigorous. Conclusions: The patient demonstrated predominantly T H2 cytokine production in vitro. Unlike other patients with HIV who have hyper-IgE and increased T H2 cytokine production, our patient has maintained HIV-specific immune responses, a low viral load, and a normal CD4 count without antiretroviral therapy. These findings support a diagnosis of primary hyper-IgE syndrome. Presence of anti-HIV–specific IgE may represent a protective mechanism against HIV replication in our patient. (J Allergy Clin Immunol 1999;104:1045-51.)