Delayed-type hypersensitivity skin testing predicts progression to AIDS in HIV-infected patients

Objective: To evaluate the prognostic significance of cutaneous delayed- type hypersensitivity (DTH) skin testing in persons infected with HIV. Design: Cohort study. Setting: United States Air Force (USAF) Medical Center. Patients: Consecutive sample of 889 HIV-infected USAF personnel or dependents undergoing their first staging evaluation from 1985 through August 1990 in the USAF HIV Natural History Study. Measurements: All patients were evaluated with DTH skin testing including purified protein derivative and four control skin test antigens: mumps, candida, tetanus toxoid, and trichophyton. In addition, all patients underwent CD4⁺ T-cell surface marker determinations. The relation between DTH skin test response at first evaluation and progression to Walter Reed stage 6 (presence of an AIDS-defining opportunistic infection) was evaluated using Kaplan-Meier survival analysis. Results: Patients with more than 400 CD4⁺ T cells/mm³ are more likely than those having fewer than 400 CD4⁺ T cells per mm³ to respond to at least one (94% compared with 67%, P < 0.001) or at least two (86% compared with 45%, P < 0.001) DTH skin tests. Mean CD4 counts are lower for anergic compared with nonanergic patients and for patients responding to a single control skin test compared with those responding to two or more skin tests (P < 0.05). The DTH skin test response at first evaluation was also found to predict progression to AIDS; the relative risk at 5 years of follow-up was 2.5 (95% CI, 1.2 to 5.2) for anergy compared with a single positive skin test and 3.0 (CI, 1.4 to 6.2) for a single compared with two or more skin test responses. The DTH skin test response at first evaluation was a predictor of progression (P < 0.001) when controlling for initial CD4 count and Walter Reed stage in a Cox proportional hazards regression analysis. Conclusions: The DTH skin test response, a functional measure of cellular immunity, is an independent predictor of progression to AIDS in persons with HIV.