Publications & Reports

Computational analysis of antibody dynamics identifies recent HIV-1 infection.

Seaton KE, Vandergrift NA, Deal AW, Rountree W, Bainbridge J, Grebe E, Anderson DA, Sawant S, Shen X, Yates NL, Denny TN, Liao HX, Haynes BF, Robb ML, Parkin N, Santos BR, Garrett N, Price MA, Naniche D, Duerr AC; CEPHIA group, Keating S, Hampton D, Facente S, Marson K, Welte A, Pilcher CD, Cohen MS, Tomaras GD.
Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.

Abstract

Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.

Link to publisher’s web site

Publication

  • Journal: JCI Insight
  • Published: 21/12/2017
  • Volume: 2
  • Issue: 24
  • Pagination: e94355

Author