Utility of the Signal-to-Cutoff Ratio and Antigen Index from Fourth- and Fifth-Generation HIV-1/HIV-2 Antigen/Antibody Assays for the Diagnosis of Acute HIV Infection: Applicability for Real-Time Use for Immediate Initiation of Antiretroviral Therapy.

Identification of individuals with acute HIV infection (AHI) and rapid initiation of antiretroviral therapy (ART) are priorities for HIV elimination efforts. Fourth- and fifth-generation HIV-1/HIV-2 antigen (Ag)/antibody (Ab) combination assays can quickly identify patients with AHI, but false-positive results can occur. Confirmatory nucleic acid amplification testing (NAAT) may not be rapidly available. We reviewed the data for 127 patients with positive fourth-generation ARCHITECT and fifth-generation Bio-Plex immunoassay results who had negative or indeterminate confirmatory Ab testing results, which yielded 38 patients with confirmed AHI and 89 patients with false-positive results. The receiver operating characteristic (ROC) curves showed excellent discriminatory power, with an area under the curve (AUC) for the signal-to-cutoff (S/CO) ratio of 0.970 (95% confidence interval [CI], 0.935 to 1.00) and an AUC for the Ag index (AI) of 0.968 (95% CI, 0.904 to 1.00). A threshold of 3.78 for the S/CO ratio would maximize the sensitivity (96.3%) and specificity (93.4%). The threshold for AI was 2.83 (sensitivity of 100% and specificity of 96.4%). The S/CO ratio was significantly correlated with the viral load (Spearman correlation coefficient, 0.486 [ P  = 0.014]), but the AI was not. The viral loads were all high, with a median of >2.8 million copies/mL. Two false-positive results with AI and S/CO ratio values markedly higher than the medians were observed, indicating that biological false-positive results can occur. Review of the S/CO ratio or AI may be used to improve the accuracy of AHI diagnosis prior to confirmatory NAAT results being available.