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

Abstract 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.