Broadly neutralizing HIV-1 antibody reactivity in HIV tests: implications for diagnostics

Objective: Passive immunization with broadly neutralizing antibodies (bNAbs) is under evaluation for HIV prevention. BNAbs target gp120 or gp41, two HIV envelope antigens commonly present in diagnostic tests. Depending on bNAb type and dose administered to humans, serum levels can reach nearly 1 mg/ml and wane over several weeks to months. We investigated the reactivity of bNAbs in HIV serological tests to inform diagnostic testing practices for persons treated with these products. Design and methods: The antigp120 bNAbs VRCO1, PGT121, PGT145, 3BNC117, 10-1074 and N6 and antigp41 bNAbs 10E8 and 10E8v4 were tested with the laboratory-based Bio-Rad Ag/Ab Combo assay, the point-of-care single-use Determine Combo, OraQuick, Reveal G4, SureCheck, Uni-Gold, INSTI and DPP HIV-1/2 assays, and the supplemental Geenius and HIV-1 Western Blot assays. Results: At 1 mg/ml, all bNAbs were nonreactive in four screening tests. OraQuick, SureCheck, Reveal G4 and INSTI detected at least two bNAbs each; SureCheck exhibited reactivity to six bNAbs. Geenius was HIV-1 indeterminate (gp160+) with all bNAbs except PGT121, which was HIV antibody-negative. HIV-1 Western Blot was indeterminate (gp41+/gp160+) with 10E8 and 10E8v4 and negative with the remaining bNAbs. There was no correlation between the test antigen construct(s) and bNAb reactivity. Conclusion: We identified a laboratory-based Ag/Ab EIA and three single-use rapid HIV tests that are nonreactive against a panel of bNAbs supporting some diagnostic tests can distinguish HIV-1 infection events among persons receiving bNAb immunoprophylaxis. Evaluation of HIV diagnostic tests prior to clinical use may identify suitable serologic assays for persons administered bNAbs.

Automated summary

The study identified several diagnostic tests that can differentiate HIV-1 infection events among persons receiving bNAb immunoprophylaxis, providing guidance for diagnostic testing practices.