Analysis of the optimal cut-point for HIV-p24 antigen testing to diagnose HIV infection in HIV-exposed children from resource-constrained settings

BackgroundNucleic-acid-testing (NAT) to diagnose HIV infection in children under age 18 months provides a barrier to HIV-testing in exposed children from resource-constrained settings. The ultrasensitive HIV-p24-antigen (Up24) assay is cheaper and easier to perform and is sensitive (84–98%) and specific (98–100%). The cut-point optical density (OD) selected for discriminating between positive and negative samples may need assessment due to regional differences in mother-to-child HIV-transmission rates.ObjectivesWe used receiver operator characteristics (ROC) curves and logistic regression analyses to assess the effect of various cut-points on the diagnostic performance of Up24 for HIV-infection status among HIV-exposed children. Positive and negative predictive values at different rates of disease prevalence were also estimated.Study designA study of Up24 testing on dried blood spot (DBS) samples collected from 278 HIV-exposed Haitian children, 3–24-months of age, in whom HIV-infection status was determined by NAT on the same DBS card.ResultsThe sensitivity and specificity of Up24 varied by the cut-point-OD value selected. At a cut-point-OD of 8-fold the standard deviation of the negative control (NCSD), sensitivity and specificity of Up24 were maximized [87.8% (95% CI, 83.9–91.6) and 92% (95% CI, 88.8–95.2), respectively]. In lower prevalence settings (5%), positive and negative predictive values of Up24 were maximal (75.9% and 98.8%, respectively) at a cut-point-OD that was 15-fold the NCSD.ConclusionsIn low prevalence settings, a high degree of specificity can be achieved with Up24 testing of HIV-exposed children when a higher cut-point OD is used; a feature that may facilitate more frequent use of Up24 antigen testing for HIV-exposed children.