title: Associations of host genetic variants on CD4⁺ lymphocyte count and plasma HIV-1 RNA in antiretroviral naïve children.
abstract: BACKGROUND
  CD4 T-lymphocyte (CD4) counts and HIV plasma RNA concentration (RNA) are 2 key HIV disease markers. The complex interplay between virus and host genetics may contribute to differences in viral set point and CD4 status. Determining the effects of host genetic variation on HIV disease markers is often complicated by the use of antiretroviral therapy. In this study, the association between genetic variants and baseline HIV RNA and CD4 counts was examined in a large cohort of antiretroviral naïve children.
  
  
  METHODS
  Specimens from 1053 HIV-infected children were screened for single nucleotide polymorphisms in 78 regions from 17 genes. Linear regression with a robust variance estimator was used to test the association between genetic markers with HIV RNA and CD4 count, controlling for age, race/ethnicity and study. False discovery rate (FDR) controlling was used to adjust for multiple testing.
  
  
  RESULTS
  The study population was 60% black, 26% Hispanic and 13% white; median age 2.35 years; 55% female. Baseline median CD4 count was 780/mm; median log10 HIV RNA was 5.17 copies/mL. For analyses of the associations of genetic makers with baseline CD4 count, 6 HLA and 4 additional markers exhibited P < 0.05, but none met the criteria for statistical significance with FDR controlled at 0.05. For baseline HIV RNA, HLA DRB1*15, DRB1*10, B-27/57, B-14, Cw-8, B-57 were statistically significant with FDR controlled at 0.05.
  
  
  CONCLUSIONS
  These results provide strong evidence that HLA DRB1*15, DRB1*10, B-27/57, B-14, Cw-8, B-57 are associated with HIV RNA and play a role in HIV pathogenesis in infected children.
authors.affiliation: From the *Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; and †University of California, San Diego, La Jolla, CA and Rady Children's Hospital, San Diego, CA.
authors.forename: Min
authors.initials: M
authors.lastname: Qin
authors.forename: Sean
authors.initials: S
authors.lastname: Brummel
authors.forename: Kumud K
authors.initials: KK
authors.lastname: Singh
authors.forename: Terence
authors.initials: T
authors.lastname: Fenton
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1; D015235:HLA-B Antigens / Q000235:genetics; D059909:HLA-B14 Antigen / Q000235:genetics; D015796:HLA-B27 Antigen / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood*
chemical_list: D015415:Biomarkers; D015235:HLA-B Antigens; D059909:HLA-B14 Antigen; D015796:HLA-B27 Antigen; C103707:HLA-B57 antigen; D015236:HLA-C Antigens; C524551:HLA-C*08 antigen; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D006649:Histocompatibility Antigens; D012367:RNA, Viral