title: A strong association of human leukocyte antigen-associated Pol and Gag mutations with clinical parameters in HIV-1 subtype A/E infection.
abstract: OBJECTIVE
  Identification of human leukocyte antigen-associated HIV-1 polymorphisms (HLA-APs) in different global populations furthers our understanding of HIV-1 pathogenesis and may help identify candidate immunogens for HIV vaccines targeted to these populations. Although numerous population-based studies identifying HLA-APs have been conducted in HIV-1 subtype B- and subtype C-infected cohorts, few have focused on subtype A/E.
  
  
  METHODS
  We investigated HLA-APs in a cohort of chronically HIV-1 subtype A/E-infected Vietnamese individuals.
  
  
  METHODS
  HLA-APs in HIV-1 Gag, Pol, and Nef regions from 388 treatment-naive individuals chronically infected with HIV-1 subtype A/E were analyzed using phylogenetically informed approaches.
  
  
  RESULTS
  A total of 303 HLA-APs were identified. HLA-APs occurring at six positions in Gag and six positions in Pol were significantly associated with higher plasma viral load (pVL), whereas HLA-APs occurring at two positions in Gag and 13 positions in Pol were significantly associated with lower CD4 T-cell counts. Furthermore, the proportion of Pol codons harboring an HLA-AP specific to the host's HLA correlated positively with HIV-1 pVL (R = 0.22; P < 0.0001) and inversely with CD4 T-cell counts (R = -0.32; P < 0.0001). Similarly, the proportion of HLA-associated Gag codons harboring host-specific HLA-AP correlated inversely with CD4 T-cell counts (R = -0.13; P = 0.01).
  
  
  CONCLUSIONS
  These significant associations between HIV-1 amino acids adapted to Vietnamese HLA alleles and higher pVL and lower CD4 T-cell counts suggests that accumulation of cytotoxic T cells escape mutations may influence clinical outcomes in HIV-1 subtype A/E-infected Vietnamese individuals.
authors.affiliation: aCenter for AIDS Research, Kumamoto University, Kumamoto, Japan beScience Group, Microsoft Research, Los Angeles, California, USA cNational Hospital of Tropical Diseases, Dong Da District, Hanoi, Vietnam dFaculty of Health Sciences, Simon Fraser University, Burnaby, BC, USA eAIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan fBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada gInternational Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan hNuffield Department of Medicine, University of Oxford, Oxford, UK. *Giang Van Tran and Takayuki Chikata contributed equally to this study.
authors.forename: Giang
authors.initials: G
authors.lastname: Van Tran
authors.forename: Takayuki
authors.initials: T
authors.lastname: Chikata
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Carlson
authors.forename: Hayato
authors.initials: H
authors.lastname: Murakoshi
authors.forename: Dung Hoai
authors.initials: DH
authors.lastname: Nguyen
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tamura
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Akahoshi
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kuse
authors.forename: Keiko
authors.initials: K
authors.lastname: Sakai
authors.forename: Sachiko
authors.initials: S
authors.lastname: Sakai
authors.forename: Kyle
authors.initials: K
authors.lastname: Cobarrubias
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Kinh
authors.initials: K
authors.lastname: Van Nguyen
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D000328:Adult; D044466:Asian People; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D008297:Male; D009154:Mutation; D010949:Plasma / Q000821:virology; D011110:Polymorphism, Genetic; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus