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

Musie Ghebremichael,Elijah Paintsil,Jack Tubbs,Haben Michael

doi:10.3844/jmssp.2019.55.64

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.

Highlights

HIV infects CD4+ T cells and leads to cell death and subsequent depletion of CD4 cells
In the US, CD4+ T cell count and HIV viral load are measured at the time of diagnosis and at least every 3-4 months on Antiretroviral therapy (ART)
The WHO recommendation for ART monitoring in low and middle income countries has evolved from CD4+ T cell monitoring every six months

Summary

Introduction

HIV infects CD4+ T cells and leads to cell death and subsequent depletion of CD4 cells. Antiretroviral therapy (ART) suppresses HIV viral replication and leads to maintenance or increase in CD4+ T cells, thereby restoring immune function. In resource-rich countries, the standard of care for monitoring ART is the routine laboratory monitoring of CD4+ T cell count and HIV viral load (Hammer et al, 2006; Mellors et al, 1997). In the US, CD4+ T cell count and HIV viral load are measured at the time of diagnosis and at least every 3-4 months on ART. These laboratory services and frequency of measurements are not routinely available in many resource-limited settings (Diagbouga et al, 2003). The WHO recommendation for ART monitoring in low and middle income countries has evolved from CD4+ T cell monitoring every six months

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