title: An additive effect of protective host genetic factors correlates with HIV nonprogression status.
abstract: BACKGROUND
  In HIV-positive individuals, complex multifactorial mechanisms control viral infection. In addition to viral and immunological factors, the host genetic background also plays an important role. Our objective was to evaluate how various genetic factors associated with delayed AIDS onset.
  
  
  METHODS
  Thirty HIV+ long-term nonprogressors (LTNPs) and 30 known progressors were analyzed. Host genes were analyzed in peripheral blood mononuclear cells DNA: CCR5 and HLA were polymerase chain reaction typed. HLA-C5', HCP5 polymorphisms, and CCL3L1 copy number were determined using real-time polymerase chain reaction.
  
  
  RESULTS
  The CCL3L1high-copy-CCR5 deletion genetic risk groups was overrepresented in LTNPs. However, separately, neither CCL3L1 nor CCR5 were significantly associated with clinical outcome. HLA seemed as a strong nonprogression determinant, mainly HLA-B and the less-studied HLA-C. HLA-Cw0102 and HLA-C5' had an impact on LTNP phenotype along with HLA-B5701 and B2705. The presence of allele combinations like HLA- B*5701-Cw0602, HLA-B*2705-Cw0102, or HLA-B*3801-Cw1203 had the strongest effect in non-progression. As for HCP5, no independent effect was observed. The studied factors had additive effects, and although the number of patients was small, it seemed that carrying a high number of protective alleles associated with progression delay.
  
  
  CONCLUSIONS
  We showed the additive load of protective host factors was predictive of nonprogression, and that HLA-associated factors were predominant in this global effect.
authors.affiliation: Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Salgado
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Simón
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sanz-Minguela
authors.forename: Norma Ibón
authors.initials: NI
authors.lastname: Rallón
authors.forename: Mariola
authors.initials: M
authors.lastname: López
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vicario
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Benito
authors.forename: Berta
authors.initials: B
authors.lastname: Rodés
mesh_terms: D000328:Adult; D019742:Chemokines, CC / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D019713:Receptors, CCR5 / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C492767:CCL3L1 protein, human; D019742:Chemokines, CC; C080521:HCP5 long noncoding RNA, human; D006680:HLA Antigens; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D019713:Receptors, CCR5