Delayed-type hypersensitivity, in vitro T-cell responsiveness and risk of active coccidioidomycosis among HIV-infected patients living in the coccidioidal endemic area

The prognostic importance of specific and general tests of immune function were examined among a cohort of 170 subjects infected with human immunodeficiency virus type-1 (HIV), living in an area endemic for the fungal infection coccidioidomycosis. Using the proportional hazards model and multivariate analysis, lack of expression of coccidioidal delayed-type hypersensitivity (DTH) was found to be dependent on anergy in response to the non-coccidioidal antigens mumps, Trichophyton and Candida (relative hazard 4.2, 95% CI 1.8-9.8, P = 0.001). Among subjects with CD4 lymphocyte counts ≥ 250 μl^-1 on entry into the study, the in vitro lymphocyte transformation (LT) response to the coccidioidal antigen toluene spherule lysate was 4967 ± 1652 (mean counts per minute (c.p.m.) ± SEM) in subjects with coccidioidal DTH compared with 136 ± 222 in those with negative DTH (P < 0.001). However, amongst those whose CD4 count was < 250 μl^-1, LT responses were low and there was no significant difference based on coccidioidal DTH (P = 0.965). Using the proportional hazards model and multivariate analysis, only a CD4 count < 250 μl^-1 was prognostically associated with the development of either active coccidioidomycosis or AIDS. These data indicate that immunodeficiency, particularly a CD4 lymphocyte count < 250 μl^-1, is the most important factor in the lack of expression of specific immunity to coccidioidomycosis and in the development of active coccidioidomycosis among HIV-infected individuals living in the coccidioidal endemic area.