Background Two manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDCapproved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance. Methods We ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays. Results The Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios. Conclusions Differences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.
|Publication status||Published - 1 Jul 2019|
Bibliographical noteFunding Information:
The Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) was supported by grants from the Bill and Melinda Gates Foundation (OPP1017716 to G.M., OPP1062806 to C.D.P. and OPP1115799). Additional support for analysis was provided by a grant from the US National Institutes of Health (R34 MH096606 to C.D.P.) and by the South African Department of Science and Technology and the National Research Foundation. Specimen and data collection were funded in part by grants from the NIH (P01 AI071713, R01 HD074511, P30 AI027763, R24 AI067039, U01 AI043638, P01 AI074621 and R24 AI106039); the HIV Prevention Trials Network (HPTN) sponsored by the NIAID, National Institutes of Child Health and Human Development (NICH/HD), National Institute on Drug Abuse, National Institute of Mental Health, and Office of AIDS Research, of the NIH, DHHS (UM1 AI068613 and R01 AI095068); the California HIV-1 Research Program (RN07-SD-702); Brazilian Program for STD and AIDS, Ministry of Health (914/BRA/3014-UNESCO); and the S?o Paulo City Health Department (2004-0.168.922- 7). Selected samples from International AIDS Vaccine Initiative (IAVI)-supported cohorts were funded by IAVI with the generous support of USAID and other donors; a full list of IAVI donors is available at www.iavi. org. S.N.F. is affiliated to Facente Consulting. Facente Consulting provided support in the form of salary for author S.N.F. but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the 'author contributions' section. N. P. is Executive Director of Data First Consulting, Inc., which received salary support for this project from the Bill and Melinda Gates Foundation through grant OPP1115799 to FIND (Geneva, Switzerland). The funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the 'author contributions' section. The funders provided support in the form of salaries for authors J.B.S., A.W., M.P.B., J.H., D.H., S.M.K., K. M., C.D.P., G.M. and E.G. but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.
© 2019 Sempa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.