Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection.
BACKGROUND
HLA-B57, as well as cytotoxic T-lymphocyte (CTL) responses restricted by this allele, have been strongly associated with long-term non-progressive chronic HIV-1 infection. However, their impact on viral replication during acute HIV-1 infection is not known.


METHODS
Clinical and immunological parameters during acute and early HIV-1 infection in individuals expressing HLA-B57 were assessed. HIV-1-specific T-cell responses were determined by peptide-specific interferon-gamma production measured using Elispot assay and flow-based intracellular cytokine quantification.


RESULTS
Individuals expressing HLA-B57 presented significantly less frequently with symptomatic acute HIV-1 infection (4/116, 3.4%) than expected from the frequency of chronically infected individuals expressing this allele (43/446, 9.6%; P < 0.05). During acute infection, virus-specific CD8 T-cell responses were dominated by HLA-B57-restricted responses, with significantly broader (P < 0.02) and stronger (P < 0.03) responses restricted by HLA-B57 than restricted by all other co-expressed HLA class I alleles combined. Six out of nine individuals expressing HLA-B57 controlled HIV-1 viremia in the absence of therapy at levels < 5000 copies/ml (median, 515 copies/ml) during up to 29 months following acute infection.


CONCLUSIONS
These data demonstrate that host genetic factors can influence the clinical manifestations of acute HIV-1 infection and provide a functional link between HLA-B57 and viral immune control.
Altfeld
Marcus
M
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
Addo
Marylyn M
MM
Rosenberg
Eric S
ES
Hecht
Frederick M
FM
Lee
Paul K
PK
Vogel
Martin
M
Yu
Xu G
XG
Draenert
Rika
R
Johnston
Mary N
MN
Strick
Daryld
D
Allen
Todd M
TM
Feeney
Margaret E
ME
Kahn
James O
JO
Sekaly
Rafick P
RP
Levy
Jay A
JA
Rockstroh
Jürgen K
JK
Goulder
Philip J
PJ
Walker
Bruce D
BD
D000208:Acute Disease; D000328:Adult; D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D016056:Immunodominant Epitopes