title: Protective Effect of HLA-B*5701 and HLA-C -35 Genetic Variants in HIV-Positive Caucasians from Northern Poland.
abstract: OBJECTIVE
  Association of two HLA class I variants with HIV-1 pretreatment viremia, CD4+ T cell count at the care-entry and CD4+ T cell nadir.
  
  
  METHODS
  414 HIV-positive Caucasians (30% women) aged 19-73 years were genotyped for HLA-C -35 (rs9264942) and HLA-B*5701 variants. HIV-1 viral load, as well as CD4+ T cell count at care-entry and nadir, were compared across alleles, genotypes and haplotypes.
  
  
  RESULTS
  HLA-C -35 C/C genotype was found in 17.6% patients, C/T genotype in 48.1%, and T/T genotype in 34.3% patients. HLA-B*5701 variant was present in 5.8% of studied population. HIV plasma viremia in the group with C allele was significantly lower (p=0.0002) compared to T/T group [mean:4.66 log (SD:1.03) vs. 5.07 (SD:0.85) log HIV-RNA copies/ml, respectively], while CD4+ T cell count at baseline was notably higher among C allele carriers compared to T/T homozygotes [median: 318 (IQR:127-537) cells/μl vs. median: 203 (IQR:55-410) cells/μl, respectively] (p=0.0007). Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390) cells/μl] was significantly higher compared to T/T group [median: 133 (IQR:46-328) cells/μl] (p=0.006). Among cases with HLA-B*5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/μl, p=0.04, respectively) compared to HLA-B*5701 negative individuals. The lowest viremia (mean: 3.85 log [SD:1.3]) HIV-RNA copies/ml and the highest baseline and nadir CD4+ T cell [median: 476 (IQR:304-682) vs. median: 361 (IQR: 205-574) cells/μl, respectively) were found in individuals with HLA-B*5701(+)/HLA-C -35 C/C haplotype.
  
  
  CONCLUSIONS
  HLA-C -35 C and HLA-B*5701 allele exert a favorable effect on the immunological (higher baseline and nadir CD4+ T cell count) and virologic (lower pretreatment HIV viral load) variables. This protective effect is additive for the compound HLA-B*5701(+)/HLA-C -35 C/C haplotype.
authors.affiliation: Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Leszczyszyn-Pynka
authors.affiliation: Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Bogusz
authors.initials: B
authors.lastname: Aksak-Wąs
authors.affiliation: Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Urbańska
authors.affiliation: Department of Infectious, Tropical Diseases and Acquired Immunodeficiency, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Miłosz
authors.initials: M
authors.lastname: Parczewski
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D012367:RNA, Viral / Q000032:analysis; D019562:Viral Load; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D015235:HLA-B Antigens; C484830:HLA-B*57:01 antigen; D015236:HLA-C Antigens; D012367:RNA, Viral