Temporal effect of HLA-B*57 on viral control during primary HIV-1 infection.
BACKGROUND
HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP).


RESULTS
Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint.


CONCLUSIONS
The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function.
Sagar A
SA
Vaidya
Hendrik
H
Streeck
Noor
N
Beckwith
Musie
M
Ghebremichael
Florencia
F
Pereyra
Douglas S
DS
Kwon
Marylyn M
MM
Addo
Jenna
J
Rychert
Jean-Pierre
JP
Routy
Heiko
H
Jessen
Anthony D
AD
Kelleher
Frederick
F
Hecht
Rafick-Pierre
RP
Sekaly
Mary
M
Carrington
Bruce D
BD
Walker
Todd M
TM
Allen
Eric S
ES
Rosenberg
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Boston, MA, USA. maltfeld@partners.org.
Marcus
M
Altfeld
D000328:Adult; D019943:Amino Acid Substitution; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D013997:Time Factors; D019562:Viral Load
D015235:HLA-B Antigens; C103707:HLA-B57 antigen