title: Extremely prolonged HIV seroconversion associated with an MHC haplotype carrying disease susceptibility genes for antibody deficiency disorders.
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 12 months 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 2 years of infection, in particular IgG(1)- and IgG(3)-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.
authors.affiliation: Infectious Diseases Unit, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Padiglione
authors.forename: Eman
authors.initials: E
authors.lastname: Aleksic
authors.forename: Martyn
authors.initials: M
authors.lastname: French
authors.forename: Alicia
authors.initials: A
authors.lastname: Arnott
authors.forename: Kim M
authors.initials: KM
authors.lastname: Wilson
authors.forename: Emma
authors.initials: E
authors.lastname: Tippett
authors.forename: Matthew
authors.initials: M
authors.lastname: Kaye
authors.forename: Lachlan
authors.initials: L
authors.lastname: Gray
authors.forename: Anne
authors.initials: A
authors.lastname: Ellett
authors.forename: Megan
authors.initials: M
authors.lastname: Crane
authors.forename: David E
authors.initials: DE
authors.lastname: Leslie
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Alan
authors.initials: A
authors.lastname: Breschkin
authors.forename: Chris
authors.initials: C
authors.lastname: Birch
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
authors.forename: Dale A
authors.initials: DA
authors.lastname: McPhee
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Crowe
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015488:HIV Antigens / Q000276:immunology; D016655:HIV Core Protein p24 / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D006679:HIV Seropositivity / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D006239:Haplotypes / Q000235:genetics*; D022362:Hepatitis A Vaccines / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D045363:Pneumocystis carinii / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology; D012367:RNA, Viral / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D013997:Time Factors; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
chemical_list: D000906:Antibodies; D057134:Antibodies, Neutralizing; D015488:HIV Antigens; D016655:HIV Core Protein p24; D022362:Hepatitis A Vaccines; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D012367:RNA, Viral; D019713:Receptors, CCR5