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Point-of-Care C-Reactive Protein Testing to Facilitate Implementation of Isoniazid Preventive Therapy for People Living With HIV

Yoon, Christina MD, MPH*; Davis, J. Lucian MD, MAS*,†; Huang, Laurence MD, MAS*,‡; Muzoora, Conrad MMed§; Byakwaga, Helen MMed§,‖; Scibetta, Colin MD; Bangsberg, David R. MD, MPH§,**,††; Nahid, Payam MD, MPH*; Semitala, Fred C. MMed, MPH‡‡; Hunt, Peter W. MD; Martin, Jeffrey N. MD, MPH; Cattamanchi, Adithya MD, MAS*,†

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 15th, 2014 - Volume 65 - Issue 5 - p 551–556
doi: 10.1097/QAI.0000000000000085
Clinical Science

Background: Symptom-based tuberculosis screening identifies less than one-third of eligible HIV-infected patients as candidates for isoniazid preventive therapy (IPT). We evaluated whether testing for C-reactive protein (CRP) improves patient selection for IPT.

Methods: We measured CRP levels (normal <10 mg/L) using a point-of-care (POC) assay on stored serum samples from HIV-infected Ugandan adults initiating antiretroviral therapy. We assessed diagnostic accuracy in reference to baseline tuberculosis status adjudicated by an expert committee and calculated net reclassification improvement to quantify the incremental discriminatory benefit of POC-CRP in determining IPT eligibility compared to the World Health Organization (WHO) symptom screen.

Results: Of 201 patients (median CD4 cell count, 137 cells/μL; interquartile range, 83–206), 5 (2.5%) had tuberculosis. Compared to the WHO symptom screen, POC-CRP had similar sensitivity (100% vs. 80%, P = 0.30) but greater specificity (21% vs. 87%, P < 0.0001) for tuberculosis. If based on the WHO symptom screen, no patients with tuberculosis but only 42 of 196 patients without tuberculosis would have been considered IPT eligible. If POC-CRP were used instead, 1 patient with tuberculosis (reclassification of cases, −20%; P = 0.32) and 129 patients without tuberculosis (reclassification of noncases, +66%; P < 0.001) would have been reclassified as IPT eligible, a net reclassification improvement of 46% (P = 0.03). In addition, POC-CRP testing would have reduced the proportion of patients without active tuberculosis requiring confirmatory tuberculosis testing (87% vs. 21%, P < 0.0001).

Conclusions: POC-CRP testing increased more than 4-fold the proportion of HIV-infected adults immediately identified as IPT eligible and decreased the proportion of patients requiring referral for further tuberculosis diagnostic testing. POC-CRP testing could substantially improve implementation of tuberculosis screening guidelines.

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*Division of Pulmonary and Critical Care Medicine, Department of Medicine,

Curry International Tuberculosis Center, and

HIV/AIDS Division, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA;

§Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda;

Department of Epidemiology and Biostatistics, University of California, San Francisco, CA;

Department of Internal Medicine, University of California, San Francisco, CA;

**Center for Global Health, Massachusetts General Hospital, Harvard Medical School, Boston, MA;

††Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Boston, MA; and

‡‡Department of Medicine, Makerere University, Kampala, Uganda.

Correspondence to: Christina Yoon, MD, MPH, Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, Room 5K1, 1001 Potrero Avenue, San Francisco, CA 94110 (e-mail:

This research was supported by a grant from the National Institutes of Health, University of California San Francisco, Gladstone Institute of Virology and Immunology Center for AIDS Research (P30 AI027763 to C.Y.) and the National Heart, Lung and Blood Institutes at the National Institutes of Health [T32 HL007185 to C.Y.]. The iCHROMA POC-CRP Reader and POC-CRP assays used in this study were donated by the manufacturer, BodiTech Med Inc., South Korea. Neither the funders nor BodiTech Med Inc., had any role in study design, data collection/analysis, decision to publish, or preparation of the manuscript.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received August 07, 2013

Accepted December 01, 2013

© 2014 by Lippincott Williams & Wilkins