Association of tuberculosis risk with the degree of tuberculin reaction in HIV-infected patients

Background: The risk of developing active tuberculosis associated with a different size of induration to purified protein derivative (PPD) has not been prospectively assessed among individuals infected with human immunodeficiency virus (HIV). The quantification of this risk is important to more appropriately identify candidates for preventive therapy for tuberculosis. Methods: A prospective, multicenter, cohort study on tuberculosis in HIV-infected patients was conducted in 23 infectious disease units in public hospitals in Italy. Two thousand six hundred ninety-five HIV-infected patients were enrolled in the study. Of these, 1054 patients who were nonanergic at the time of entry were included in the present analysis. The median duration of follow-up was 102 weeks. The main outcome measure was a diagnosis of active tuberculosis confirmed by the isolation of Mycobacterium tuberculosis in culture. Results: Among the 252 patients with PPD reactivity, patients with an induration to PPD of 2 to 4 mm had a median CD4(+) lymphocyte count of 0.34x10(9)/L (interquartile [IQ] range, 0.14x10(9)-0.56x10(9)), those with a response of 5 to 9 mm had a median count of 0.38x10(9)/L (IQ range, 0.24x10(9)-0.56x10(9)), and those with a response of 10 mm or higher had a median count of 0.37x10(9)/L (IQ range, 0.23x10(9)-0.52x10(9)) (P=.38). Compared with the 802 nonanergic PPD-negative patients, hazard ratios of tuberculosis were 2.1 (95% confidence interval [CI], 0.2-18.3) among the 55 patients with a response to PPD of 2 to 4 mm, 5.7 (95% CI, 1.6-19.8) among the 128 patients with a response to PPD of 5 to 9 mm, and 23.1 (95% CI, 7.8-68.6) among the 69 patients with a response to PPD of 10 mm or higher. Conclusions: Among nonanergic HIV-infected patients, the degree of response to tuberculin does not appear to reflect the degree of immunosuppression and is strongly correlated with the subsequent incidence of tuberculosis. To identify HIV-infected patients who are at an increased risk of tuberculosis and may benefit from preventive therapy, a response to PPD of 5 mm appears to be an appropriate cutoff point.