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Incidence of Tuberculosis in the United States among HIV-Infected Persons

Norman Markowitz, MD; Nellie I. Hansen, MPH; Philip C. Hopewell, MD; Jeffrey Glassroth, MD; Paul A. Kvale, MD; Bonita T. Mangura, MD; Timothy C. Wilcosky, PhD; Jeanne M. Wallace, MD; Mark J. Rosen, MD; and Lee B. Reichman, MD, MPH
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The Pulmonary Complications of HIV Infection Study Group Grant Support: In part by contract NO1-HR-76033 and grant RO1 HL48511-02 from the National Heart, Lung, and Blood Institute. Cosponsored by the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Requests for Reprints: Norman Markowitz, MD, Division of Infectious Diseases, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202. Current Author Addresses: Drs. Markowitz and Kvale: Division of Infectious Diseases, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;126(2):123-132. doi:10.7326/0003-4819-126-2-199701150-00005
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Background: The resurgence of tuberculosis in the United States is largely linked to the human immunodeficiency virus (HIV) epidemic. Despite this link, the epidemiology of tuberculosis and preventive strategies in patients infected with HIV are not completely understood.

Objectives: To determine the incidence and predictors of tuberculosis in HIV-infected persons.

Design: Prospective, multicenter cohort study.

Setting: Community-based cohort of persons with and without HIV infection at centers in the eastern, midwestern, and western United States.

Participants: 1130 HIV-seropositive patients without AIDS who were followed for a median of 53 months (814 homosexual men, 261 injection drug users, and 55 women who had acquired HIV through heterosexual contact).

Measurements: Delayed hypersensitivity response to purified protein derivative (PPD) tuberculin and mumps antigen, CD4 T-lymphocyte counts, and frequency of tuberculosis.

Results: 31 HIV-seropositive patients developed tuberculosis (0.7 cases per 100 person-years [95% CI, 0.5 to 1.0]). The most important demographic risk factor was location (adjusted risk ratio for eastern compared with midwestern and western United States, 4.1 [CI, 2.0 to 8.4]). Tuberculosis occurred more frequently in persons with CD4 counts of less than 200 cells/mm3 (1.2 cases per 100 person-years [CI, 0.7 to 1.9]) than in those with higher counts (0.5 cases per 100 person-years [CI, 0.3 to 0.8]). The rate of tuberculosis was highest among tuberculin converters (5.4 cases per 100 person-years [CI, 1.1 to 15.7]), lower among patients who were PPD positive at first testing (4.5 cases per 100 person-years [CI, 1.6 to 9.7]), and lowest among patients who remained PPD negative (0.4 cases per 100 person-years [CI, 0.2 to 0.7]). Tuberculosis was not reported among persons who had PPD reactions of 1 to 4 mm. Compared with that of patients who tested positive for mumps, the risk for tuberculosis of those who tested negative was increased about sevenfold if they were PPD positive (P < 0.03) and fourfold if they were PPD negative (P < 0.02).

Conclusions: Incidence of tuberculosis was higher in the eastern United States, in patients with CD4 counts of less than 200 cells/mm3, and in PPD-positive patients. Analysis of tuberculin reaction size supports the current interpretive criteria of the Centers for Disease Control and Prevention. Nonreactivity to mumps antigen indicated increased risk for tuberculosis independent of PPD response.


tuberculosis ; hiv


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Figure 1.
Estimated time to death for HIV-seropositive persons who received a diagnosis of tuberculosis.3333P

The solid line represents patients whose last CD4 count before the diagnosis of tuberculosis was 200 cells/mm or more; the broken line represents patients whose count was less than 200 cells/mm . Sample sizes at baseline and at 12 and 24 months are shown in parentheses. Among patients with CD4 counts of 200 cells/mm or more, 7 persons died and the 12-month survival rate was 92%. Among patients with CD4 counts of less than 200 cells/mm , 10 persons died and the 12-month survival rate was 34%. This difference in mortality was significant ( = 0.02 by log-rank test).

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Figure 2.
Incidence of tuberculosis in HIV-seropositive patients by size of purified protein derivative tuberculin induration.

Height of bars represents the rate of tuberculosis (in cases per 100 person-years) for each group. The numbers above the bars are the rates (in cases per 100 person-years), 95% CIs, and numbers of persons who received a diagnosis of tuberculosis/total number of persons.

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