Human leukocyte antigens and HIV type 1 viral load in early and chronic infection: predominance of evolving relationships.
BACKGROUND
During untreated, chronic HIV-1 infection, plasma viral load (VL) is a relatively stable quantitative trait that has clinical and epidemiological implications. Immunogenetic research has established various human genetic factors, especially human leukocyte antigen (HLA) variants, as independent determinants of VL set-point.


RESULTS
To identify and clarify HLA alleles that are associated with either transient or durable immune control of HIV-1 infection, we evaluated the relationships of HLA class I and class II alleles with VL among 563 seroprevalent Zambians (SPs) who were seropositive at enrollment and 221 seroconverters (SCs) who became seropositive during quarterly follow-up visits. After statistical adjustments for non-genetic factors (sex and age), two unfavorable alleles (A*3601 and DRB1*0102) were independently associated with high VL in SPs (p<0.01) but not in SCs. In contrast, favorable HLA variants, mainly A*74, B*13, B*57 (or Cw*18), and one HLA-A and HLA-C combination (A*30+Cw*03), dominated in SCs; their independent associations with low VL were reflected in regression beta estimates that ranged from -0.47+/-0.23 to -0.92+/-0.32 log(10) in SCs (p<0.05). Except for Cw*18, all favorable variants had diminishing or vanishing association with VL in SPs (p<or=0.86).


CONCLUSIONS
Overall, each of the three HLA class I genes had at least one allele that might contribute to effective immune control, especially during the early course of HIV-1 infection. These observations can provide a useful framework for ongoing analyses of viral mutations induced by protective immune responses.
Tang
Jianming
J
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America. jtang@uab.edu
Malhotra
Rakhi
R
Song
Wei
W
Brill
Ilene
I
Hu
Liangyuan
L
Farmer
Paul K
PK
Mulenga
Joseph
J
Allen
Susan
S
Hunter
Eric
E
Kaslow
Richard A
RA
D000328:Adult; D000367:Age Factors; D000483:Alleles; D002908:Chronic Disease; D005260:Female; D014644:Genetic Variation; D006679:HIV Seropositivity; D015497:HIV-1 / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D012044:Regression Analysis; D016036:Seroepidemiologic Studies; D019562:Viral Load; D015024:Zambia
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II