title: HLA alleles are associated with altered risk for disease progression and central nervous system impairment of HIV-infected children.
abstract: OBJECTIVE
  To examine the effects of human leukocyte antigen (HLA) alleles on HIV-1-related disease progression and central nervous system (CNS) impairment in children.
  
  
  METHODS
  Five hundred seventy-two HIV-1-infected children, identified as disease progressors or nonprogressors, were selected from PACTG P152 and P300 through a case-cohort sampling scheme. Study endpoints were HIV-1-related disease progression-free survival and time to CNS impairment.
  
  
  METHODS
  DNA was genotyped for HLA alleles using a Luminex 100 platform. Weighted Kaplan-Meier methods, and Cox proportional hazards models were used to assess the effects of HLA alleles on study endpoints.
  
  
  RESULTS
  Presence of the B-27 allele (n = 20) was associated with complete protection against disease progression and CNS impairment over the median follow-up of 26 months (P < 0.0001 for both). These findings held in multivariate analyses controlling for baseline covariates including race, gender, age, log HIV-1 RNA, CD4 lymphocyte count and percent, weight for age z score and treatment, and for other genotypes shown to affect HIV-1-related disease progression. Also, although the Cw-2 allele protected against disease progression [Hazard ratio (HR), 0.48; 95% confidence interval (CI): 0.28 to 0.81; P = 0.006], the A-24 allele was associated with more rapid CNS impairment (HR: 2.01; 95% CI: 1.04 to 3.88; P = 0.04). The HLA class II DQB1-2 allele was associated with a delayed disease progression (HR: 0.66; 95% CI: 0.47-0.92; P = 0.01) and CNS impairment (HR: 0.58; 95% CI: 0.36 to 0.93; P = 0.02).
  
  
  CONCLUSIONS
  Presence of B-27, Cw-2, or DQB1-2 alleles was associated with delayed HIV-1 disease progression, while B-27, A-24, and DQB1-2 alleles were associated with altered progression to CNS impairment in children.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, CA 92093-0672, USA. kusingh@ucsd.edu
authors.forename: Kumud K
authors.initials: KK
authors.lastname: Singh
authors.forename: Ping Kathryn
authors.initials: PK
authors.lastname: Gray
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Terence
authors.initials: T
authors.lastname: Fenton
authors.forename: Rodney N
authors.initials: RN
authors.lastname: Trout
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002493:Central Nervous System Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D016133:Polymerase Chain Reaction
chemical_list: D004279:DNA, Viral; D006680:HLA Antigens