title: Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load.
abstract: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL<51 copies/ml and on CD4(+) T-cell recovery after initiation of combination antiretroviral therapy (cART).
  
  
  
  We genotyped the rs2395029 (A>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects.
  
  
  
  The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95% confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART.
  
  
  
  The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART.
authors.affiliation: Dept. of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: lise.wegner.thoerner@regionh.dk.
authors.forename: Lise Wegner
authors.initials: LW
authors.lastname: Thørner
authors.affiliation: Dept. of Clinical Immunology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Erikstrup
authors.affiliation: Dept. of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Lene Holm
authors.initials: LH
authors.lastname: Harritshøj
authors.affiliation: Dept. of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Margit Hørup
authors.initials: MH
authors.lastname: Larsen
authors.affiliation: Dept. of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.affiliation: Dept. of Infectious Diseases, Odense University Hospital, Odense, Denmark.
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.affiliation: Dept. of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark.
authors.forename: Carsten Schade
authors.initials: CS
authors.lastname: Larsen
authors.affiliation: Dept. of Infectious Diseases, Aarhus University Hospital, Aalborg, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Pedersen
authors.affiliation: Dept. of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.affiliation: Dept. of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.affiliation: Dept. of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
mesh_terms: D000328:Adult; D000483:Alleles; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D003718:Denmark; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000276:immunology; D019562:Viral Load / Q000187:drug effects / Q000235:genetics* / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D004268:DNA-Binding Proteins; C080521:HCP5 long noncoding RNA, human; D015236:HLA-C Antigens; C406241:POLR1H protein, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated
keywords: Disease progression; HIV; Host genetics; Immune reconstitution; Viral load