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 < 10mg/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 (NRI) to quantify the incremental discriminatory benefit of POC-CRP in determining IPT-eligibility compared to the WHO symptom screen. Results—Of 201 patients (median CD4 cell-count 137 cells/μL, IQR 83-206), five (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 42/196 patients without tuberculosis would have been considered IPT-eligible. If POC-CRP were used instead, one patient with tuberculosis (reclassification of cases -20%, p=0.32) and 129 patients without tuberculosis (reclassification of non-cases +66%, p<0.001) would have been reclassified as IPT-eligible, an NRI 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%, Conclusions—POC-CRP testing increased more than four-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