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

Abstract Background Nucleic-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. Objectives We 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 design A 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. Results The 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. Conclusions In 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.