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.

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to disclose.

Figures

Figure 1. Patient flow diagram

Overall, 223 HIV-infected adults initiating ART were enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort from May 2007 and April 2009, all of whom had stored baseline serum available for this analysis. We excluded two patients missing baseline symptom data, five patients receiving TB treatment at the time of study enrollment, and 15 patients with unknown six-month TB status (six withdrew study consent, two were lost to follow-up [LTFU] and seven died). Thus, 201 patients were included in this analysis.

Figure 2. Reclassification of patients eligible for isoniazid preventive therapy

If isoniazid preventive therapy (IPT) eligibility were determined by the WHO symptom screen, no patients with active TB but only 42 of 196 patients without active TB would have been considered eligible for IPT. If point-of-care C-reactive protein (POC-CRP) were used instead, one patient with active TB (reclassification of cases = -20%, p=0.32) and 129 patients without active TB (reclassification of non-cases = +66%, p