Favorable and unfavorable HLA class I alleles and haplotypes in Zambians predominantly infected with clade C human immunodeficiency virus type 1.
The setpoint of viral RNA concentration (viral load [VL]) during chronic human immunodeficiency virus type 1 (HIV-1) infection reflects a virus-host equilibration closely related to CD8(+) cytotoxic T-lymphocyte (CTL) responses, which rely heavily on antigen presentation by the human major histocompatibility complex (MHC) (i.e., HLA) class I molecules. Differences in HIV-1 VL among 259 mostly clade C virus-infected individuals (137 females and 122 males) in the Zambia-UAB HIV Research Project (ZUHRP) were associated with several HLA class I alleles and haplotypes. In particular, general linear model analyses revealed lower log(10) VL among those with HLA allele B*57 (P = 0.002 [without correction]) previously implicated in favorable response and in those with HLA B*39 and A*30-Cw*03 (P = 0.002 to 0.016); the same analyses also demonstrated higher log(10) VL among individuals with A*02-Cw*16, A*23-B*14, and A*23-Cw*07 (P = 0.010 to 0.033). These HLA effects remained strong (P = 0.0002 to 0.075) after adjustment for age, gender, and duration of infection and persisted across three orders of VL categories (P = 0.001 to 0.084). In contrast, neither B*35 (n = 15) nor B*53 (n = 53) showed a clear disadvantage such as that reported elsewhere for these closely related alleles. Other HLA associations with unusually high (A*68, B*41, B*45, and Cw*16) or low (B*13, Cw*12, and Cw*18) VL were either unstable or reflected their tight linkage respecting disequilibria with other class I variants. The three consistently favorable HLA class I variants retained in multivariable models and in alternative analyses were present in 30.9% of subjects with the lowest (<10,000 copies per ml) and 3.1% of those with the highest (>100,000) VL. Clear differential distribution of HLA profiles according to level of viremia suggests important host genetic contribution to the pattern of immune control and escape during HIV-1 infection.
Department of Medicine, University of Alabama at Birmingham, Alabama 35294, USA.
Jianming
J
Tang
Shenghui
S
Tang
Elena
E
Lobashevsky
Angela D
AD
Myracle
Ulgen
U
Fideli
Grace
G
Aldrovandi
Susan
S
Allen
Rosemary
R
Musonda
Richard A
RA
Kaslow
D000328:Adult; D000483:Alleles; D005260:Female; D005805:Genes, MHC Class I; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D012367:RNA, Viral / Q000097:blood; D014766:Viremia / Q000235:genetics / Q000276:immunology / Q000821:virology; D015024:Zambia
D006680:HLA Antigens; D012367:RNA, Viral