Abstract
Background Custom staging assays, including the Sedia HIV-1 Limiting Antigen Avidity EIA (LAg) and avidity modifications of the Ortho VITROS anti-HIV-1+2 and Abbott ARCHITECT HIV Ag/Ab Combo assays, are used to identify ‘recent’ infections in clinical settings and for cross-sectional HIV incidence estimation. However, the high dynamic range of chemiluminescent platforms allows differentiating recent and longstanding infection on signal intensity, and this raises the prospect of using unmodified diagnostic assays for infection timing and surveillance applications.
Methods We tested a panel of 2,500 well-characterised specimens with estimable duration of HIV infection with the three assays and the unmodified ARCHITECT. Regression models were used to estimate mean durations of recent infection (MDRI), context-specific false-recent rates (FRR) and correlation between signal intensity and LAg measurements. A hypothetical epidemiological scenario was constructed to evaluate utility in surveillance applications.
Results Over a range of MDRIs (reflecting recency discrimination thresholds), a diluted ARCHITECT-based RITA produced lower FRRs than the VITROS platform (FRR ≈ 0.5% and 1.5% respectively at MDRI of 200 days) and the unmodified diagnostic ARCHITECT produces incidence estimates with comparable precision to LAg (RSE ≈ 17.5% and 15% respectively at MDRI of 200 days). ARCHITECT S/CO measurements were highly correlated with LAg ODn measurements (r = 0.80) and values below 200 are strongly predictive of LAg recency and duration of infection less than one year.
Conclusions Low quantitative measurements from the unmodified ARCHITECT obviate the need for additional recency testing and its use is feasible in clinical staging and incidence surveillance applications.
Footnotes
Previous presentation: Portions of these data presented at the 2016 HIV Diagnostics Conference, Atlanta, GA, March 24, 2016 and at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, WA, February 13-16, 2017.
Conflicts of Interest and Sources of Funding: All authors, as members or collaborators of the Consortium for the Evaluation and Performance of Incidence Assays (CEPHIA), are supported by a grant from the Bill and Melinda Gates Foundation (OPP1017716). Additional support for analysis was provided by a grant from the US National Institutes of Health (R34MH096606) and specimen and data collection were funded in part by additional grants from the NIH (P01 AI071713, R01 HD074511, P30 AI027763, R24 AI067039, AI43638, AI74621 and AI106039); California HIV-1 Research Program (RN07-SD-702); Brazilian Program for STD and AIDS, Ministry of Health (914/BRA/3014-UNESCO); and São Paulo City Health Department (2004-0.168.922–7). S.M.K and M.P.B. have received and/or receive ongoing grant support from Abbott, Ortho Clinical Diagnostics and Sedia Biosciences Corporation for the evaluation of their respective assays. M.A.P. and selected samples from IAVI supported cohorts are funded by IAVI with the generous support of USAID and other donors; a full list of IAVI donors is available at www.iavi.org.
Collaborators: The Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) is comprised of the authors and: Tom Quinn, Oliver Laeyendecker (Johns Hopkins University); David Burns (National Institutes of Health); Anita Sands (World Health Organization); Tim Hallett (Imperial College London); Sherry Michele Owen, Bharat Parekh, Connie Sexton (Centers for Disease Control and Prevention); Anatoli Kamali (International AIDS Vaccine Initiative); Reshma Kassanjee (Univeristy of Cape Town); David Matten, Hilmarié Brand, Trust Chibawara (South African Centre for Epidemiological Modelling and Analysis); Gareth Priede, Jarryd Gerber, Andrew Powrie (Implicit Design); Elaine McKinney (Public Health England); Mila Lebedeva, Dylan Hampton (Blood Systems Research Institute); Lisa Loeb (The Options Study – University of California, San Francisco); Steven G Deeks, Rebecca Hoh (The SCOPE Study – University of California, San Francisco); Zelinda Bartolomei, Natalia Cerqueira (The AMPLIAR Cohort – University of São Paulo); Breno Santos, Kellin Zabtoski, Rita de Cassia Alves Lira (The AMPLIAR Cohort – Grupo Hospital Conceição); Rosa Dea Sperhacke, Leonardo R Motta, Machline Paganella (The AMPLIAR Cohort – Universidade Caxias Do Sul); Helena Tomiyama, Claudia Tomiyama, Priscilla Costa, Maria A Nunes, Gisele Reis, Mariana M Sauer, Natalia Cerqueira, Zelinda Nakagawa, Lilian Ferrari, Ana P Amaral, Karine Milani (The São Paulo Cohort – University of São Paulo, Brazil); Salim S Abdool Karim, Quarraisha Abdool Karim, Thumbi Ndungu, Nigel Garret, Nelisile Majola, Natasha Samsunder (CAPRISA, University of KwaZulu-Natal); Denise Naniche (The GAMA Study – Barcelona Centre for International Health Research); Inácio Mandomando, Eusebio V Macete (The GAMA Study – Fundacao Manhica); Jorge Sanchez, Javier Lama (SABES Cohort – Asociación Civil Impacta Salud y Educación (IMPACTA)); Ann Duerr (The Fred Hutchinson Cancer Research Center); Maria R Capobianchi (National Institute for Infectious Diseases “L. Spallanzani”, Rome); Barbara Suligoi (Istituto Superiore di Sanità, Rome); Susan Stramer (American Red Cross); Phillip Williamson (Creative Testing Solutions / Blood Systems Research Institute); Marion Vermeulen (South African National Blood Service); and Ester Sabino (Hemocentro do Sao Paolo).
Journal submission: This is a pre-print (before review, acceptance or editing) of an article submitted to the Journal of Acquired Immune Deficiency Syndrome.