title: Host genetic factors associated with symptomatic primary HIV infection and disease progression among Argentinean seroconverters.
abstract: BACKGROUND
  Variants in HIV-coreceptor C-C chemokine receptor type 5 (CCR5) and Human leukocyte antigen (HLA) genes are the most important host genetic factors associated with HIV infection and disease progression. Our aim was to analyze the association of these genetic factors in the presence of clinical symptoms during Primary HIV Infection (PHI) and disease progression within the first year.
  
  
  METHODS
  Seventy subjects diagnosed during PHI were studied (55 symptomatic and 15 asymptomatic). Viral load (VL) and CD4 T-cell count were evaluated. HIV progression was defined by presence of B or C events and/or CD4 T-cell counts <350 cell/mm3. CCR5 haplotypes were characterized by polymerase chain reaction and SDM-PCR-RFLP. HLA-I characterization was performed by Sequencing.
  
  
  RESULTS
  Symptoms during PHI were significantly associated with lower frequency of CCR5-CF1 (1.8% vs. 26.7%, p = 0.006). Rapid progression was significantly associated with higher frequency of CCR5-CF2 (16.7% vs. 0%, p = 0.024) and HLA-A*11 (16.7% vs. 1.2%, p = 0.003) and lower frequency of HLA-C*3 (2.8% vs. 17.5%, p = 0.035). Higher baseline VL was significantly associated with presence of HLA-A*11, HLA-A*24, and absence of HLA-A*31 and HLA-B*57. Higher 6-month VL was significantly associated with presence of CCR5-HHE, HLA-A*24, HLA-B*53, and absence of HLA-A*31 and CCR5-CF1. Lower baseline CD4 T-cell count was significantly associated with presence of HLA-A*24/*33, HLA-B*53, CCR5-CF2 and absence of HLA-A*01/*23 and CCR5-HHA. Lower 6-month CD4 T-cell count was associated with presence of HLA-A*24 and HLA-B*53, and absence of HLA-A*01 and HLA-B*07/*39. Moreover, lower 12-month CD4 T-cell count was significantly associated with presence of HLA-A*33, HLA-B*14, HLA-C*08, CCR5-CF2, and absence of HLA-B*07 and HLA-C*07.
  
  
  CONCLUSIONS
  Several host factors were significantly associated with disease progression in PHI subjects. Most results agree with previous studies performed in other groups. However, some genetic factor associations are being described for the first time, highlighting the importance of genetic studies at a local level.
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.
authors.forename: Romina Soledad
authors.initials: RS
authors.lastname: Coloccini
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.
authors.forename: Dario
authors.initials: D
authors.lastname: Dilernia
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.
authors.forename: Yanina
authors.initials: Y
authors.lastname: Ghiglione
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Turk
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina; Hospital Juan A. Fernandez, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Laufer
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubio
authors.affiliation: Hospital Juan A. Fernandez, Buenos Aires, Argentina; Fundación Huésped, Buenos Aires, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Socías
authors.affiliation: Hospital Juan A. Fernandez, Buenos Aires, Argentina; Fundación Huésped, Buenos Aires, Argentina.
authors.forename: María Inés
authors.initials: MI
authors.lastname: Figueroa
authors.affiliation: Hospital Juan A. Fernandez, Buenos Aires, Argentina; Fundación Huésped, Buenos Aires, Argentina.
authors.forename: Omar
authors.initials: O
authors.lastname: Sued
authors.affiliation: Hospital Juan A. Fernandez, Buenos Aires, Argentina; Fundación Huésped, Buenos Aires, Argentina.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Salomón
authors.affiliation: Laboratorio de Biología Celular y Retrovirus, CONICET, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangano
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Pando
mesh_terms: D001118:Argentina; D015153:Blotting, Western; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D006679:HIV Seropositivity / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D058605:Host-Derived Cellular Factors / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D019713:Receptors, CCR5 / Q000235:genetics*; D019562:Viral Load
chemical_list: C584933:CCR5 protein, human; D006680:HLA Antigens; D058605:Host-Derived Cellular Factors; D019713:Receptors, CCR5