title: KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy.
abstract: BACKGROUND
  In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART) have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR) and their ligands class I human leukocyte antigen (HLA), could influence immunological response to cART.
  
  
  METHODS
  KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+) T-cell count <200/mm(3)) and full responders (FR, N = 104, CD4(+) T-cell count >350/mm(3)). Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics.
  
  
  RESULTS
  The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005). The functional compound genotype HLA-C1(+)/KIR2DL3(+), even at multivariable analysis, when adjusted for nadir CD4(+) T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals) 0.34 (0.13-0.88), P = 0.03.
  
  
  CONCLUSIONS
  Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy. a.soria@hsgerardo.org
authors.forename: Alessandro
authors.initials: A
authors.lastname: Soria
authors.forename: Franca Rosa
authors.initials: FR
authors.lastname: Guerini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bandera
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bolognesi
authors.forename: Alessia
authors.initials: A
authors.lastname: Uglietti
authors.forename: Caterina
authors.initials: C
authors.lastname: Fusco
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zucchi
authors.forename: Renato
authors.initials: R
authors.lastname: Maserati
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D006680:HLA Antigens
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