Potential Utility of C-reactive Protein for Tuberculosis Risk Stratification among Patients with Non-Meningitic Symptoms at HIV Diagnosis in Low- and Middle-Income Countries

ABSTRACT Article Summary We assessed the association between C-reactive protein (CRP) and Mycobacterium tuberculosis (TB) diagnosis in symptomatic patients at HIV diagnosis. We found that CRP concentrations can improve tuberculosis risk stratification, facilitating decision making about whether (specific) tuberculosis testing is indicated before antiretroviral therapy initiation. Background The World Health Organization recommends initiating same-day ART while tuberculosis testing is underway for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve tuberculosis risk stratification in this population. Methods In this baseline analysis of 498 adults (>18 years) with tuberculosis symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP (≥3 mg/dL) using generalized linear models. Results Eighty-seven (17.5%) patients were diagnosed with baseline TB. The median CRP was 33.0 mg/L (IQR: 5.1, 85.5) in those with TB, and 2.6 mg/L (IQR: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4%, and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART, and 0.8% to 5.0% would have untreated TB at ART initiation. Conclusions CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3-fold to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.