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Analysis of the optimal cut-point for HIV-p24 antigen testing to diagnose HIV infection in HIV-exposed children from
1Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Insights
Optimizing the ultrasensitive HIV-p24-antigen (Up24) assay cut-point improves HIV diagnosis in exposed children. Higher cut-points enhance specificity in low-prevalence settings, aiding wider Up24 use.
Area of Science:
- Pediatric infectious diseases
- Diagnostic assay development
- Global health
Background:
- Nucleic-acid-testing (NAT) for diagnosing HIV in children under 18 months is a barrier in resource-limited settings.
- The ultrasensitive HIV-p24-antigen (Up24) assay offers a cheaper, easier alternative with high sensitivity and specificity.
- Optimal cut-point optical density (OD) selection for Up24 may vary by regional HIV transmission rates.
Purpose of the Study:
- To assess how different cut-points affect the diagnostic performance of the Up24 assay for HIV infection in exposed children.
- To evaluate the impact of cut-point selection on sensitivity, specificity, and predictive values.
- To estimate positive and negative predictive values at varying disease prevalence rates.
Main Methods:
- Utilized receiver operator characteristic (ROC) curves and logistic regression analyses.
- Tested dried blood spot (DBS) samples from 278 HIV-exposed Haitian children aged 3-24 months.
- Compared Up24 results with NAT as the gold standard for determining HIV infection status.
Main Results:
- Up24 sensitivity and specificity were dependent on the selected cut-point OD.
- Maximal sensitivity (87.8%) and specificity (92%) were achieved at an 8-fold negative control standard deviation (NCSD) cut-point.
- In 5% prevalence settings, maximal positive (75.9%) and negative (98.8%) predictive values occurred at a 15-fold NCSD cut-point.
Conclusions:
- A higher cut-point OD for Up24 testing enhances specificity in low-prevalence settings.
- Optimized Up24 cut-points can facilitate increased utilization of this assay for HIV diagnosis in exposed children.
- This approach may improve HIV screening accessibility in resource-constrained environments.
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.
