Comparison of Two Htlv-I/Ii Small Platform Assays Potentially Suitable for Tissue Donor Screening in the United States

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Background: Human T-cell lymphotrophic virus (HTLV) type I has been linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I associated myelopathy (HAM). Transmission of HTLV by blood and organ transplantation has been documented, with some infections leading to clinical disease. Since December 31, 2009 organ donors in the US are no longer tested for anti-HTLV antibodies. This decision was prompted, at least in part, by discontinuation of Abbott HTLV-I/II EIA and absence of a suitable FDA-approved replacement. However, tissue donors are still being tested for HTLV-I/II using a combination of validated research assays or large platform test (PRIZM). Confirmatory testing is not routinely performed, and the number of false positive organ donors is unknown. Aim: To share our experience with 2 HTLV-I/II EIAs currently in FDA application process. Method: We evaluated multiple lots of Avioq HTLV-I/II (RUO) EIA (Avioq, Inc., Research Triangle Park, NC) and MP Diagnostics HTLV I/II 4.1 ELISA System (IUO) (MP Biomedicals, Irwine, CA). The Avioq EIA (RUO) utilizes antigens derived from purified and inactivated HTLV-I viral lysate, a purified HTLV-II viral lysate, and a recombinant HTLV-I p21E antigen. The MP Bio EIA (IUO) uses recombinant proteins gp46-I, gp46-II, GD21 and MGK. The recombinant envelope proteins are derived from the central region of the external glycoprotein of the respective HTLV-I and HTLV-II gp46. We tested at least 3 lots of each assay using a panel of well pedigreed specimens with known HTLV-I/II status including 11 specimens with false positive or indeterminate HTLV-I/II reactivity. We also tested “in real time” 1700 tissue donors' specimens by Avioq and 4811 tissue donors by MP Bio EIA. Results: Both assays passed and performed comparably with our evaluation panel. In contrast to the discontinued Abbott EIA that incorrectly identified 10/11 difficult specimens both Avioq and MPBio EIAs correctly called 10/11 false positive and indeterminate specimens (see Table below). However, during “real time” testing we observed that the Avioq assay consistently detected HTLV-I/II reactive donors 4 times (1.53% v. 0.37% respectively, p< 0.0001) more often as the MP Bio assay. When we tested randomly chosen subset of Avioq reactive specimens with HTLV Western Blot none of the specimens were confirmed.Table: [Assays Performance with Evaluation Panel]Conclusions: Both prospective HTLV-I/II assays performed better than the discontinued Abbott HTLV-I/II EIA and offer significantly improved performance for anti-HTLV-I/II antibodies screening. Only one company (MP Bio) offers HTLV-I/II EIA and HTLV-I/II WB with subtyping. Careful consideration of screening HTLV-I/II assay will prevent unnecessary donor loss.