title: Point-of-care C-reactive protein testing to facilitate implementation of isoniazid preventive therapy for people living with HIV.
abstract: 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.
authors.affiliation: *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.
authors.forename: Christina
authors.initials: C
authors.lastname: Yoon
authors.forename: J Lucian
authors.initials: JL
authors.lastname: Davis
authors.forename: Laurence
authors.initials: L
authors.lastname: Huang
authors.forename: Conrad
authors.initials: C
authors.lastname: Muzoora
authors.forename: Helen
authors.initials: H
authors.lastname: Byakwaga
authors.forename: Colin
authors.initials: C
authors.lastname: Scibetta
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: Payam
authors.initials: P
authors.lastname: Nahid
authors.forename: Fred C
authors.initials: FC
authors.lastname: Semitala
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Adithya
authors.initials: A
authors.lastname: Cattamanchi
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis*; D019411:Clinical Laboratory Techniques / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D019095:Point-of-Care Systems; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000175:diagnosis* / Q000517:prevention & control
chemical_list: D000995:Antitubercular Agents; D002097:C-Reactive Protein; D007538:Isoniazid