PMID- 25715101
OWN - NLM
STAT- MEDLINE
DCOM- 20151030
LR  - 20150226
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 29
IP  - 5
DP  - 2015 Mar 13
TI  - The HLA-C*04: 01/KIR2DS4 gene combination and human leukocyte antigen alleles 
      with high population frequency drive rate of HIV disease progression.
PG  - 507-17
LID - 10.1097/QAD.0000000000000574 [doi]
AB  - OBJECTIVE: The objective of this study is to identify human leukocyte antigen 
      (HLA) class I and killer-cell immunoglobulin-like receptor (KIR) genotypes 
      associated with different risks for HIV acquisition and HIV disease progression. 
      DESIGN: A cross-sectional study of a cohort of 468 high-risk individuals (246 
      HIV-positive and 222 HIV-negative) from outpatient clinics in Lima (Peru). 
      METHODS: The cohort was high-resolution HLA and KIR-typed and analysed for 
      potential differences in single-allele frequencies and allele combinations 
      between HIV-positive and HIV-negative individuals and for associations with HIV 
      viral load and CD4 cell counts in infected individuals. RESULTS: HLA class I 
      alleles associated with a lack of viral control had a significantly higher 
      population frequency than relatively protective alleles (P = 0.0093), in line 
      with a rare allele advantage. HLA-A02 : 01 and HLA-C04 : 01 were both associated 
      with high viral loads (P = 0.0313 and 0.0001, respectively) and low CD4 cell 
      counts (P = 0.0008 and 0.0087, respectively). Importantly, the association 
      between HLA-C04 : 01 and poor viral control was not due to its linkage 
      disequilibrium with other HLA alleles. Rather, the coexpression of its putative 
      KIR ligand KIR2DS4f was critically linked to elevated viral loads. CONCLUSION: 
      These results highlight the impact of population allele frequency on viral 
      control and identify a novel association between HLA-C04 : 01 in combination with 
      KIR2DS4f and uncontrolled HIV infection. Our data further support the importance 
      of the interplay of markers of the adaptive and innate immune system in viral 
      control.
FAU - Olvera, Alex
AU  - Olvera A
AD  - aIrsiCaixa AIDS Research Institute - HIVACAT, Hospital Germans Trias i 
      bUniversitat Autonoma de Barcelona, Barcelona, Spain cDepartment of Medicine, 
      David Geffen School of Medicine at University of California Los Angeles, Los 
      Angeles, California, USA dAsociacion Civil IMPACTA Salud y Educacion, Lima, Peru 
      eDepartment of Global Health, University of Washington, Seattle, Washington 
      fUniversity of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA 
      gResearch Institute of the McGill University Health Centre, Montreal, Quebec, 
      Canada hDepartament d'Estadistica i Investigacio Operativa, Universitat 
      Politecnica de Catalunya iInstitucio Catalana de Recerca i Estudis Avancats 
      (ICREA), Barcelona jUniversitat de Vic (UVIC-UCC), Vic, Spain. *Alex Olvera and 
      Susana Perez-Alvarez contributed equally to this work.
FAU - Perez-Alvarez, Susana
AU  - Perez-Alvarez S
FAU - Ibarrondo, Javier
AU  - Ibarrondo J
FAU - Ganoza, Carmela
AU  - Ganoza C
FAU - Lama, Javier R
AU  - Lama JR
FAU - Lucchetti, Aldo
AU  - Lucchetti A
FAU - Cate, Steven
AU  - Cate S
FAU - Hildebrand, William
AU  - Hildebrand W
FAU - Bernard, Nicole
AU  - Bernard N
FAU - Gomez, Lupe
AU  - Gomez L
FAU - Sanchez, Jorge
AU  - Sanchez J
FAU - Brander, Christian
AU  - Brander C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-C*04 antigen)
RN  - 0 (KIR2DS4 protein, human)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - CD4 Lymphocyte Count
MH  - Cross-Sectional Studies
MH  - *Disease Progression
MH  - Gene Frequency
MH  - *Genetic Predisposition to Disease
MH  - HIV Infections/*genetics/immunology/*pathology/virology
MH  - HLA-C Antigens/*genetics
MH  - Humans
MH  - Peru
MH  - Receptors, KIR/*genetics
MH  - Viral Load
EDAT- 2015/02/26 06:00
MHDA- 2015/10/31 06:00
CRDT- 2015/02/26 06:00
PHST- 2015/02/26 06:00 [entrez]
PHST- 2015/02/26 06:00 [pubmed]
PHST- 2015/10/31 06:00 [medline]
AID - 00002030-201503130-00001 [pii]
AID - 10.1097/QAD.0000000000000574 [doi]
PST - ppublish
SO  - AIDS. 2015 Mar 13;29(5):507-17. doi: 10.1097/QAD.0000000000000574.