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Computational analysis of antibody dynamics identifies recent HIV-1 infection.
Seaton, Kelly E; Vandergrift, Nathan A; Deal, Aaron W; Rountree, Wes; Bainbridge, John; Grebe, Eduard; Anderson, David A; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L; Denny, Thomas N; Liao, Hua-Xin; Haynes, Barton F; Robb, Merlin L; Parkin, Neil; Santos, Breno R; Garrett, Nigel; Price, Matthew A; Naniche, Denise; Duerr, Ann C; Keating, Sheila; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D; Cohen, Myron S; Tomaras, Georgia D.
Affiliation
  • Seaton KE; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Vandergrift NA; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Deal AW; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Rountree W; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Bainbridge J; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Grebe E; South African Centre for Epidemiological Modelling and Analysis, Stellenbosch University, Stellenbosch, South Africa.
  • Anderson DA; Burnet Institute, Melbourne, Victoria, Australia.
  • Sawant S; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Shen X; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Yates NL; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Denny TN; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Liao HX; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Haynes BF; Duke Human Vaccine Institute, Department of Medicine, Durham, North Carolina, USA.
  • Robb ML; Department of Immunology, Duke University, Durham, North Carolina, USA.
  • Parkin N; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
  • Santos BR; Foundation for Innovative New Diagnostics, Geneva, Switzerland; Data First Consulting, Belmont, California, USA.
  • Garrett N; The Evaluation of Prevention Methods Linked to Acute and Recent Infection (AMPLIAR) Cohort Group Hospital Conceição is detailed in the Supplemental Acknowledgments.
  • Price MA; Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
  • Naniche D; International AIDS Vaccine Initiative, San Francisco, California, USA.
  • Duerr AC; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
  • Keating S; Vaccine and Infectious Disease and Public Health Science Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Facente S; Blood Systems Research Institute, San Francisco, California, USA.
  • Marson K; Blood Systems Research Institute, San Francisco, California, USA.
  • Welte A; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Pilcher CD; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Cohen MS; South African Centre for Epidemiological Modelling and Analysis, Stellenbosch University, Stellenbosch, South Africa.
  • Tomaras GD; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, California, USA.
JCI Insight ; 2(24)2017 12 21.
Article in En | MEDLINE | ID: mdl-29263306
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Antibodies / HIV Infections / HIV-1 Type of study: Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: JCI Insight Year: 2017 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Antibodies / HIV Infections / HIV-1 Type of study: Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: JCI Insight Year: 2017 Document type: Article Affiliation country: