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Risk Factors for Tuberculosis in HIV-lnfected PersonsA Prospective Cohort Study
Giorgio Antonucci, MD;
Enrico Girardi, MD;
Mario C. Raviglione, MD;
Giuseppe Ippolito, MD;
for the Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA);
Paolo Almi, MD;
Gioacchino Angarano, MD;
Orlando Armignacco, MD;
Sergio Babudieri, MD;
Nazario Bevilacqua, MD;
Alessandra Bini, MD;
Patrizia Bottura, MD;
Evangelo Boumis, MD;
Paolo Costigliola, MD;
Antonio Chirianni, MD;
Giovanni Di Perri, MD;
Isabella Errante, MD;
Marco Libanore, MD;
Elio Manzillo, MD;
Lorenzo Minoli, MD;
Pasquale Narciso, MD;
Gabriella Pagano, MD;
Gianpietro Pellizzer, MD;
Elisabetta Rapiti, MD, MPH;
Stefano Rusconi, MD;
Domenico Santoro, MD;
Eliana Savalli, MD;
Marcello Tavio, MD;
Antonio Traverso, MD;
Pierluigi Viale, MD
JAMA. 1995;274(2):143-148.
Abstract
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Objective.
—To analyze how demographic, clinical, and laboratory characteristics influence the risk of tuberculosis in human immunodeficiency virus (HIV)— infected individuals; to examine the incidence of tuberculosis associated with change in skin test responsiveness in HIV-infected, tuberculin-negative, nonanergic individuals.
Design.
—Multicenter cohort study.
Setting.
—Twenty-three infectious disease units in public hospitals in Italy.
Subjects.
—A consecutive sample of 3397 HIV-infected subjects were considered for entry in the study. Of these, 2695 who were followed up for at least 4 weeks were enrolled in the study; 739 subjects (27.4%) were unavailable for follow-up. The median duration of follow-up was 91 weeks.
Main Outcome Measure.
—Culture-proven tuberculosis.
Results.
—Eighty-three episodes of tuberculosis were observed. Incidence rates of tuberculosis were 5.42 per 100 person-years among tuberculin-positive subjects, 3.00 per 100 person-years among anergic subjects, and 0.45 per 100 person-years among tuberculin-negative nonanergic subjects. In multivariate analysis, being tuberculin-positive (hazard ratio [HR], 9.94; 95% confidence interval [CI], 3.84 to 25.72) or anergic (HR, 3.35; 95% CI, 1.40 to 8.00), or having a CD4+ lymphocyte count less than 0.20x 109/L (HR, 4.87; 95% CI, 2.35 to 10.11) or between 0.20 and 0.35x109/L (HR, 2.35; 95% CI, 1.09 to 5.05) were statistically significantly associated with the risk of tuberculosis. Incidence of tuberculosis increased with decreasing levels of CD4+ lymphocytes in the three groups of subjects with different skin test responsiveness. Skin tests were repeated 1 year after enrollment in 604 tuberculin-negative nonanergic subjects; three cases of tuberculosis were observed among the 13 subjects who converted to tuberculin reactivity.
Conclusions.
—Risk of tuberculosis in HIV-infected persons can be more precisely quantified by jointly considering skin test reactivity and CD4+ lymphocyte count. Periodic skin tests in tuberculin-negative nonanergic individuals can be useful in identifying individuals at high risk of active tuberculosis.
(JAMA. 1995;274:143-148)
Author Affiliations
S. Maria Scala, Siena; Policlinico, Bari; L. Spallanzani I Divisione, Rome; SS. Annunziata, Sassari; Gemelli, Rome; Pizzardi, Bologna; Civile, Busto Arsizio; L. Spallanzani, Rome; S. Orsola, Bologna; II Policlinico, Naples; Civile Maggiore, Verona; Niguarda, Milan; S. Anna, Ferrara; Cotugno, Naples; S. Matteo, Pavia; L. Spallanzani II Divisione, Rome; S. Martino, Genoa; S. Bortolo, Vicenza; OER Lazio, Rome; Sacco Clinica, Milan; S. Anna, Como; Cisanello, Pisa; Centro Oncologico, Aviano; USL 1, Aosta; Civile, Piacenza.
From the Centro di Riferimento AIDS, Ospedale L. Spallanzani, Rome, Italy (Drs Antonucci, Girardi, and Ippolito), and Tuberculosis Programme, World Health Organization, Geneva, Switzerland (Dr Raviglione).
Footnotes
A complete list of the members of the Gruppo Italiano di Studio Tubercolosi e AIDS (GISTA) appears at the end of this article.
Reprint requests to Centro di Riferimento AIDS, Ospedale L. Spallanzani, Via Portuense 292, 00149 Rome, Italy (Dr Antonucci).
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