An improved HIV antigen/antibody prototype assay for earlier detection of acute HIV infection

Background: Early detection of acute HIV infection by HIV antigen/antibody assays depends on antigen sensitivity. Maintaining consistently high sensitivity across diverse HIV strains is critical to ensure equal detection. Objectives: The performance of an improved HIV antigen/antibody prototype, HIV Combo Next, was evaluated for detection of genetically-diverse HIV strains and seroconversion samples. Study design: Antigen sensitivity of the prototype was evaluated and compared to five FDA-approved HIV antigen/antibody assays using World Health Organization (WHO) HIV p24 antigen standard and reference panels, 17 virus isolates and 9 seroconversion panels. Antibody sensitivity and assay specificity of the prototype were also assessed with 1062 disease-staged and genotyped samples, and samples from 3000 blood donors and 955 individuals with low-risk for HIV infection. Results: Compared with other assays evaluated, the prototype demonstrated the best analytical sensitivity for WHO antigen standard, reference panels including 12 HIV-1 variants (0.04 – 0.25 IU/ml) and one HIV-2 variant, and 17 HIV virus isolates including HIV-1 group M, N, P and O and HIV-2 (0.3 -16 pg/ml). The enhanced sensitivity was also observed for seroconversion samples, detecting more PCR-positive samples with detection up to 7 days earlier than the other assays. Improvement in antigen sensitivity did not compromise antibody sensitivity or assay specificity, detecting all HIV disease-staged and genotyped samples, with assay specificity of 99.97% for blood donors and 99.68% for the low-risk population. Conclusions: These data indicate that the new prototype HIV Combo Next assay will be of diagnostic value, providing improved early detection for acute HIV infection from divergent HIV strains.