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

Background:The World Health Organization recommends initiating same-day antiretroviral therapy (ART) while tuberculosis (TB) testing is under way for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve TB risk stratification in this population. Methods:In this baseline analysis of 498 adults (>18 years) with TB 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 as a continuous variable using generalized linear models. Results:Eighty-seven (17.5%) participants were diagnosed with baseline TB. The median CRP was 33.0 mg/L (interquartile range: 5.1, 85.5) in those with TB, and 2.6 mg/L (interquartile range: 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- to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.