B-058 Multicenter Evaluation of the new Access HIV Ag/Ab combo Assay With Highly Sensitive HIV-1 p24 Antigen Detection on the DxI 9000 Access Immunoassay Analyzer

Abstract Background Beckman Coulter developed a fully automated Access HIV Ag/Ab combo assay for the new DxI 9000 Access Immunoassay analyzer that reports separate results for HIV-1 p24 antigen (Ag) and HIV-1/2 antibody (Ab) with a 30 minute time to first result and a sample volume of only 60 µL. Evaluation of the Access HIV Ag/Ab combo assay assessed analytical sensitivity for seroconversion panels, HIV-1 p24 Ag (WHO I.S. NIBSC code 90/636), and HIV-1 and HIV-2 Ag from different viral strains. Clinical specificity and sensitivity of this 4th generation assay was also assessed. Methods Thirty commercially available seroconversion panels were assessed on Access HIV Ag/Ab combo (3 lots), Abbott Architect HIV Ag/Ab Combo, and Roche Elecsys HIV Duo assays. The HIV-1 p24 Ag analytical sensitivity of the Access assay was performed on dilutions of HIV-1 p24 Ag WHO I.S. prepared in HIV negative human serum and plasma, ranging from 0.1 to 1.0 IU/mL. Fifty positive viral lysates from HIV-1 group M (A-H subtypes, CRF01, CRF02, CRF06, CRF11, CRF14, CRF15, CRF18, CRF36), HIV-1 group O (H and T subgroups), and HIV-2 (groups A and B) were spiked into HIV negative human CPD plasma and tested on both the Access and Architect assays. Clinical sensitivity and specificity were determined for the Access assay using the Architect assay as comparator by testing samples from HIV low risk, high risk and HIV known positive populations at three US clinical laboratories. An HIV 1/2 differentiation assay and HIV-1 RNA PCR were also run to confirm patient infection status. Results The Access HIV Ag/Ab combo assay detected a higher number of bleeds (n=90) than the Elecsys (n = 80) and Architect (n = 77) assays due to earlier Ag detection. The average number of days between positive detection of a bleed previously identified Nucleic Acid Test (NAT) positive compared to these assays was reduced by 1.2 to 1.6 days (Access = 6.8 days; Elecsys = 8.0 days; Architect = 8.4 days). The Access assay also offered a limit of detection for the HIV-1 p24 Ag WHO I.S. between 0.19 and 0.22 IU/mL and a higher sensitivity for HIV-1 p24 Ag compared to the Architect assay: overall median Signal/Cut-Off (S/CO) for the 46 HIV-1 strains = 2.45 with the Access assay when the Architect assay S/CO was normalized at 1.00. HIV-2 strains were not included in this calculation since they were not detected by the Architect assay. A clinical validation study demonstrated 100.0% sensitivity for Access (n= 1,787; 95% CI: 99.8-100.0%) vs 99.8% for the Architect assay (n=1,786; 95% CI: 99.5-99.9%) and 99.7% specificity for Access (n=8,467; 95% CI: 99.5-99.8%) vs 98.8% for the Architect assay (n= 8,467, 95% CI: 98.6-99.0). Conclusions The new Access HIV Ag/Ab combo assay demonstrated excellent analytical performances, particularly its high HIV-1 p24 Ag sensitivity, which could help reduce the diagnosis window and thus prevent any delay of treatment for an infected patient. Furthermore, the Access assay showed clinical sensitivity and specificity performance meeting or exceeding that of currently marketed HIV combo immunoassays.