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Neil M. H. Graham, MBBS, MD, MPH; Kenrad E. Nelson, MD; Liza Solomon, DrPH; Margaret Bonds, RN; Rosetta T. Rizzo, BSN; Joseph Scavotto; Jacqueline Astemborski, MHS; David Vlahov, PhD

JAMA. 1992;267(3):369-373.

Abstract
Objectives.
—To identify differences in purified protein derivative (PPD) tuberculin positivity and skin test anergy rates by human immunodeficiency virus (HIV) serostatus, CD4⁺ lymphocyte count, and other risk factors in intravenous drug users (IVDUs); and to evaluate the appropriateness of the Centers for Disease Control (CDC)—recommended definition for a positive PPD tuberculin skin test result in HIV-1—seropositive patients.

Design.
—Nested case-control and cross-sectional analyses.

Setting.
—Community-based cohort of IVDUs.

Patients.
—Two hundred sixty HIV-1—seropositive and —seronegative IVDUs, drawn from an unselected cohort, were skin-tested for sensitivity to PPD tuberculin, mumps, and Candida antigens using the Mantoux method.

Outcome Measures.
—Positivity to PPD tuberculin, skin test anergy.

Results.
—Even using the CDC definition of an induration 5 mm or greater in diameter in HIV-1 seropositives, this group was substantially less likely to be PPD tuberculin positive than HIV-1 seronegatives (13.8% vs 25.2%; P=.02). In the HIV-1 seropositives the relative odds of being PPD positive varied depending on whether 10 mm or greater (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.2 to 0.7), 5 mm or greater (OR, 0.5; 95% CI, 0.2 to 0.9), or 2 mm or greater (OR, 0.7; 95% CI, 0.4 to 1.3) was used to define a positive test result. The mean diameter induration in the HIV-1—seropositive group was 2.6 mm vs 5.4 mm in the seronegative group (P =.005). Skin test anergy (to mumps and Candida) appeared to explain the differential. Anergy was substantially higher in the HIV-1 seropositive group and increased as the CD4⁺ lymphocyte count fell (² for linear trend, 24.5; P<.0001). An inverse linear trend for PPD positivity and CD4⁺ lymphocyte count was also observed (² for trend, 6.1; P =.01). In multivariate analyses, being 35 years of age or older and being HIV-1 seronegative were significantly associated with PPD positivity, while history of previous police arrest was of borderline significance. Only HIV-1 seropositivity was significantly associated with anergy.

Conclusions.
—There findings show that CDC-recommended definition of an induration 5 mm or greater in diameter for PPD tuberculin positivity in HIV-1 seropositives significantly underestimates the "true" infection rate (using the PPD positivity rate in HIV-1 seronegatives as the criterion standard). A definition of 2 mm or greater would appear to be a better cutoff for reducing misclassification in HIV-1 seropositives. This study also confirms that delayed-type hypersensitivity is seriously depressed in HIV-1 seropositive IVDUs and that anergy testing is mandatory to properly assess a negative PPD test result.

(JAMA. 1992;267:369-373)

Author Affiliations
From the Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public Health (Drs Graham, Nelson, Solomon, and Vlahov and Ms Astemborski), and Department of Medicine, The Johns Hopkins University School of Medicine (Drs Graham, Nelson, and Vlahov), Baltimore, Md; and Baltimore City Department of Health (Mss Bonds and Rizzo and Mr Scavotto).

Footnotes
Reprint requests to Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public Health, 624 N Broadway, Baltimore, MD 21205 (Dr Graham).

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