title: HIV diversity as a biomarker for HIV incidence estimation: including a high-resolution melting diversity assay in a multiassay algorithm.
abstract: Multiassay algorithms (MAAs) can be used to estimate cross-sectional HIV incidence. We previously identified a robust MAA that includes the BED capture enzyme immunoassay (BED-CEIA), the Bio-Rad Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high-resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). The MAAs that were evaluated included the BED-CEIA, the Bio-Rad Avidity assay, viral load, and the HRM diversity assay, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. The performance characteristics based on the proportion of samples that were classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. The cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up. HIV diversity is a useful biomarker for estimating HIV incidence. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored blood plasma or serum samples without a requirement for CD4 cell count data.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Cousins
authors.forename: Jacob
authors.initials: J
authors.lastname: Konikoff
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: Richard D
authors.initials: RD
authors.lastname: Moore
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: Joelle
authors.initials: J
authors.lastname: Brown
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Koblin
authors.forename: Darrell
authors.initials: D
authors.lastname: Wheeler
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Justman
authors.forename: Sally L
authors.initials: SL
authors.lastname: Hodder
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Ron
authors.initials: R
authors.lastname: Brookmeyer
authors.forename: Susan H
authors.initials: SH
authors.lastname: Eshleman
mesh_terms: D000465:Algorithms; D015415:Biomarkers; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000821:virology*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D015994:Incidence; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D044366:Transition Temperature; D014481:United States / Q000453:epidemiology; D019562:Viral Load / Q000379:methods
chemical_list: D015415:Biomarkers