Short communicationAnalysis of the optimal cut-point for HIV-p24 antigen testing to diagnose HIV infection in HIV-exposed children from resource-constrained settings
Section snippets
Background
The World Health Organization recommends highly active antiretroviral therapy (HAART) for all children diagnosed with HIV infection at two years of age and younger.1 HAART for HIV-infected children in resource-constrained settings (RCSs) is hindered by limited access to nucleic acid testing (NAT) required for diagnosis. Frequent HIV-testing of infants with ongoing exposure to HIV through breast-feeding is also deterred. Evaluation of ultrasensitive p24 (Up24) antigen assays on liquid or dried
Objective
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 to correctly classify HIV-infection status among HIV-exposed children. Positive and negative predictive values at different rates of disease prevalence were also estimated.
Study design
As part of the JHPIEGO-UNICEF and Caris, Early Infant Diagnosis (EID) program in Haiti, DBS (Whatman # 903 cards; Fischer Scientific, MA) were collected on 278 HIV-exposed, Haitian children between 0.1 and 24 months of age for testing by HIV DNA polymerase chain reaction (HIV-DNA PCR; AMPLICOR HIV-1 DNA test version 1.5; Roche Diagnostics GMBH, Germany). Testing was done in a laboratory in Kenya accredited for infant HIV testing. This laboratory also participates in an external quality
Results
The cohort of 278 children were at a median age of four months (IQR: 2.0–7.7 months) at the time of DBS collection. Samples were stored for a median of 14 months (IQR: 11.4–15.7 months; range 7–26 months) before testing with the Up24 assay. The HIV-infection prevalence was 14.7% by HIV-DNA PCR testing. The median age of the 41 HIV-infected infants was four months (IQR: 2.2–7.4 months).
Fig. 1 shows the distribution of adjusted OD values for HIV-exposed children who tested positive or negative by
Discussion
In this study of 278 HIV-exposed children for whom the prevalence of HIV infection was determined at 14.5% by HIV-DNA PCR, we found that the sensitivity and specificity of Up24 testing on DBS samples varied significantly based on the cut-point selected. When the Youden index (8-fold NCSD) was used, sensitivity and specificity of Up24 was 88% and 92%, respectively. The cut-point identified by ROC curves was similar to that identified using AUC and logistic regression analyses. By increasing the
Conflicts of interest
The authors do not have an association that might pose a conflict of interest.
Sources of financial support
This work was funded by ICTR award (D.P.) made possible through grant number UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH”. The work was also supported by the National Institutes of Health grant # R01HD057784 (D.P.).
Acknowledgments
We thank the study participants, the Haitian Ministry of Health, and the CARIS Foundation for making this study possible. The study was approved by the Institutional Review Board at Johns Hopkins University with waiver of consent, and also by the Haitian Ministry of Health and the CARIS Foundation, the EID implementing partner.
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