Comparing the Diagnostics Accuracy of CD4+ T-Lymphocyte Count and Percent as a Surrogate Markers of Pediatric HIV Disease

Abstract

The percentage CD4+ T-lymphocytes is used to monitor pediatric HIV disease. However, in resource-limited settings, enumerating the percentage of CD4+ T-lymphocytes is hampered by the lack of laboratory infrastructure and trained technicians. In this paper, we investigated the performances of the percentage and absolute CD4+ T-lymphocytes as markers of pediatric HIV disease progression using data from HIV-infected children enrolled through the Yale Prospective Longitudinal Pediatric Cohort study. A Lehmann family of Receiver Operating Characteristic (ROC) curves were used to estimate and compare the performance of the two biomarkers in monitoring pediatric HIV disease progression. The area under the ROC (AUC) curve and its empirical estimator have previously been used to assess the performance of biomarkers for a cross-sectional data. However, there is a paucity of literature on the AUC for correlated longitudinal biomarkers. Previous works on the estimation and inference of the AUC for longitudinal biomarkers have largely focused on independent biomarkers or failed to consider the effect of covariates. The Lehmann approach allowed us to estimate the AUC of the aforementioned correlated longitudinal biomarkers as functions of explanatory variables. We found that the overall performance of the two biomarkers was comparable. The area under the ROC curves for CD4+ T cell count and percentage were 0.681 [SE = 0.029; 95% CI: 0.624-0.737] and 0.678 [SE = 0.024; 95% CI:0.630-0.725], respectively. Our results suggest that absolute CD4+ T-lymphocyte counts could be used as a proxy for percentage of CD4+ T-lymphocytes in monitoring pediatric HIV in resource-limited settings.