Extremely prolonged HIV seroconversion associated with an MHC haplotype carrying disease susceptibility genes for antibody deficiency disorders

Alex Padiglione, Eman Aleksic, Martyn French, Alicia Arnott, Kim M. Wilson, Emma Tippett, Matthew Kaye, Lachlan Gray, Anne Ellett, Megan Crane, David E Leslie, Sharon R. Lewin, Alan Breschkin, Chris Birch, Paul R. Gorry, Dale A. McPhee, Suzanne M. Crowe

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2 Citations (Scopus)

Abstract

Severe immunodeficiency during primary human immunodeficiency virus (HIV) infection is unusual. Here, we characterized viral and immunological parameters in a subject presenting with Pneumocystis jirovecii pneumonia in the setting of prolonged primary HIV illness and delayed seroconversion. HIV antibody was only detected by enzyme-linked immunosorbent assay 12months after presentation, and Western blot profiles remain indeterminate. Isolated virus was of R5 phenotype, exhibited poor viral fitness, but was otherwise unremarkable. Analysis of HIV antibody isotypes showed failure to mount a detectable HIV IgG response over nearly 2years of infection, in particular IgG1- and IgG3-specific responses, despite normal responses to common infections and vaccines. Genetic analysis demonstrated homozygosity for part of an MHC haplotype containing susceptibility genes for common variable immunodeficiency (CVID) syndrome and other antibody deficiency disorders. Thus, a primary disorder of specific antibody production may explain exceptionally slow antibody development in an otherwise severe seroconversion illness. This highlights the need for multiparameter testing, in particular use of a fourth generation HIV test, for confirming HIV infection and underscores the importance of host factors in HIV pathogenesis.

Original languageEnglish
Pages (from-to)199-208
Number of pages10
JournalClinical Immunology
Volume137
Issue number2
DOIs
Publication statusPublished - Nov 2010

Keywords

  • CVID
  • HIV
  • Pneumocystis jirovecii
  • Seroconversion

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