HLA-B*57 versus HLA-B*81 in HIV-1 infection: slow and steady wins the race?
Two human leukocyte antigen (HLA) variants, HLA-B*57 and -B*81, are consistently known as favorable host factors in human immunodeficiency virus type 1 (HIV-1)-infected Africans and African-Americans. In our analyses of prospective data from 538 recent HIV-1 seroconverters and cross-sectional data from 292 subjects with unknown duration of infection, HLA-B*57 (mostly B*57:03) and -B*81 (exclusively B*81:01) had mostly discordant associations with virologic and immunologic manifestations before antiretroviral therapy. Specifically, relatively low viral load (VL) in HLA-B*57-positive subjects (P ≤ 0.03 in various models) did not translate to early advantage in CD4(+) T-cell (CD4) counts (P ≥ 0.37). In contrast, individuals with HLA-B*81 showed little deviation from the normal set point VL (P > 0.18) while maintaining high CD4 count during early and chronic infection (P = 0.01). These observations suggest that discordance between VL and CD4 count can occur in the presence of certain HLA alleles and that effective control of HIV-1 viremia is not always a prerequisite for favorable prognosis (delayed immunodeficiency). Of note, steady CD4 count associated with HLA-B*81 in HIV-1-infected Africans may depend on the country of origin, as observations differed slightly between subgroups enrolled in southern Africa (Zambia) and eastern Africa (Kenya, Rwanda, and Uganda).
Department of Epidemiology, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA.
Heather A
HA
Prentice
Travis R
TR
Porter
Matthew A
MA
Price
Emmanuel
E
Cormier
Dongning
D
He
Paul K
PK
Farmer
Anatoli
A
Kamali
Etienne
E
Karita
Shabir
S
Lakhi
Eduard J
EJ
Sanders
Omu
O
Anzala
Pauli N
PN
Amornkul
Susan
S
Allen
Eric
E
Hunter
Richard A
RA
Kaslow
Jill
J
Gilmour
Jianming
J
Tang
D000351:Africa, Eastern; D000704:Analysis of Variance; D044383:Black People; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D015235:HLA-B Antigens / Q000378:metabolism*; D058605:Host-Derived Cellular Factors / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D019562:Viral Load / Q000276:immunology*; D015024:Zambia; D001741:Black or African American
D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D058605:Host-Derived Cellular Factors