CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Amy Carpenter Aquino
June 2019—Abbott unveiled a new and improved fourth-generation prototype HIV assay at the 2019 HIV Diagnostics Conference in March.
In an Abbott-funded study, the prototype assay was compared with the fourth-generation Abbott Architect HIV Ag/Ab Combo and Roche Elecsys HIV Combi PT run on the Cobas e602. It demonstrated broad detection of HIV-1 and HIV-2 genotypes with enhanced p24 analytic sensitivity and a reduction of the seroconversion window. The prototype assay was also found to have high specificity with minimized heterophilic antibody interference.
‘This fourth-generation prototype assay is designed to detect highly infectious people who may be missed by existing tests.’ Xiaoxing Qiu, PhD
Xiaoxing Qiu, PhD, a key developer of the prototype, presented data evaluating the performance of the prototype against current on-market Architect and Elecsys assays with the WHO International HIV-1 p24 standard, 14 commercial seroconversion panels, and an antigen-positive panel composed of four specimens from acute HIV-1 infections and 17 genetically diverse HIV-1 and HIV-2 virus isolates. The comparative evaluations took place at Abbott and in the Department of Pathology, Johns Hopkins Medical Institutions.
The analytic sensitivity of the prototype assay (0.20 IU/mL) was fourfold better than those of the Architect (0.80 IU/mL) and Elecsys (0.86 IU/mL) assays with the WHO p24 standard, said Dr. Qiu, who is a research fellow, Volwiler Society, Infectious Disease Research and Product Development, Abbott.
“Studies have demonstrated that a fourth-generation test such as Architect HIV Ag/Ab Combo can detect up to 83 percent of acute HIV infections missed by third-generation antibody-only assays,” Dr. Qiu tells CAP TODAY. “The fourfold increased analytical sensitivity of Abbott’s new, improved prototype assay suggests this assay can detect a higher percentage of acute HIV infections relative to Architect and Elecsys.”
John R. Hackett Jr., PhD, divisional vice president, Abbott Applied Research and Technology, attributed the higher sensitivity to a combination of factors, one of which is a redesign of the recombinant proteins used to drive the assay performance.
Says Dr. Qiu: “Maintaining antigen detection sensitivity for genetically diverse HIV strains is dependent upon the quality of monoclonal antibodies used by fourth-generation tests. For improving detection of HIV-2 antigen, we selected the monoclonal antibodies recognizing highly conserved epitopes between HIV-1 and HIV-2.”
Originally, she says, a biotin-streptavidin capture method was used to improve the prototype’s sensitivity. After the Food and Drug Administration issued its safety warning in 2017 about biotin interfering with laboratory results, “we redesigned the prototype without using the biotin-streptavidin capture method.”
In the evaluation of the assay’s ability to detect diluted HIV-1 antigen genotypes, the prototype assay “demonstrated enhanced analytical sensitivity across all 15 HIV-1 strains, including the highly divergent group N, P, and O isolates,” Dr. Qiu says. The enhanced antigen sensitivity (1.6–5.3-fold) suggests the assay is “designed to offer the best-in-class fourth-generation test for detection of acute infection from divergent HIV strains.”
Cases of several diverse HIV strains escaping detection in fourth-generation tests have been reported, she says. “Studies also demonstrated that the antigen sensitivity of some fourth-generation and antigen-only tests was impacted by HIV genetic diversity, particularly with HIV-1 non-B subtypes.”
The prototype assay also outperformed the Architect and Elecsys assays in detecting HIV-2 antigen subtypes. The sensitivity of the prototype assay was more than 10-fold higher than that for the Elecsys assay and more than 100-fold higher than that for the Architect assay. “Although clinical utility of HIV-2 antigen remains to be discovered because acute HIV-2 infection is rarely identified, the prototype assay may help improve detection of acute HIV-2 infection as this test detects the HIV-2 p26 protein, as well as antibodies to HIV-2,” Dr. Qiu says.
The seroconversion sensitivity of the prototype assay was consistently higher than that of the other two assays. It detected 10 of 14 panels two to eight days earlier than the Architect and Elecsys tests.
U.S. and WHO guidelines recommend starting antiretroviral therapy as soon as possible, including immediately after diagnosis of HIV infection. “By being designed to detect HIV infection earlier,” Dr. Qiu says, “the prototype assay can play a role in saving critical time for people enrolling in effective antiretroviral therapy.”