title: Seroconverting blood donors as a resource for characterising and optimising recent infection testing algorithms for incidence estimation.
abstract: BACKGROUND
  Biomarker-based cross-sectional incidence estimation requires a Recent Infection Testing Algorithm (RITA) with an adequately large mean recency duration, to achieve reasonable survey counts, and a low false-recent rate, to minimise exposure to further bias and imprecision. Estimating these characteristics requires specimens from individuals with well-known seroconversion dates or confirmed long-standing infection. Specimens with well-known seroconversion dates are typically rare and precious, presenting a bottleneck in the development of RITAs.
  
  
  METHODS
  The mean recency duration and a 'false-recent rate' are estimated from data on seroconverting blood donors. Within an idealised model for the dynamics of false-recent results, blood donor specimens were used to characterise RITAs by a new method that maximises the likelihood of cohort-level recency classifications, rather than modelling individual sojourn times in recency.
  
  
  RESULTS
  For a range of assumptions about the false-recent results (0% to 20% of biomarker response curves failing to reach the threshold distinguishing test-recent and test-non-recent infection), the mean recency duration of the Vironostika-LS ranged from 154 (95% CI: 96-231) to 274 (95% CI: 234-313) days in the South African donor population (n = 282), and from 145 (95% CI: 67-226) to 252 (95% CI: 194-308) days in the American donor population (n = 106). The significance of gender and clade on performance was rejected (p-value = 10%), and utility in incidence estimation appeared comparable to that of a BED-like RITA. Assessment of the Vitros-LS (n = 108) suggested potentially high false-recent rates.
  
  
  CONCLUSIONS
  The new method facilitates RITA characterisation using widely available specimens that were previously overlooked, at the cost of possible artefacts. While accuracy and precision are insufficient to provide estimates suitable for incidence surveillance, a low-cost approach for preliminary assessments of new RITAs has been demonstrated. The Vironostika-LS and Vitros-LS warrant further analysis to provide greater precision of estimates.
authors.affiliation: South African DST/NRF Centre for Epidemiological Modelling and Analysis, University of Stellenbosch, Stellenbosch, South Africa. r.kassanjee@gmail.com
authors.forename: Reshma
authors.initials: R
authors.lastname: Kassanjee
authors.forename: Alex
authors.initials: A
authors.lastname: Welte
authors.forename: Thomas A
authors.initials: TA
authors.lastname: McWalter
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Keating
authors.forename: Marion
authors.initials: M
authors.lastname: Vermeulen
authors.forename: Susan L
authors.initials: SL
authors.lastname: Stramer
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
mesh_terms: D000465:Algorithms; D001782:Blood Donors; D005260:Female; D006679:HIV Seropositivity / Q000453:epidemiology*; D006801:Humans; D007118:Immunoassay; D015994:Incidence; D008297:Male; D013019:South Africa / Q000453:epidemiology