HLA-B alleles associate consistently with HIV heterosexual transmission, viral load, and progression to AIDS, but not susceptibility to infection.
OBJECTIVE
HLA class I polymorphism is known to affect the rate of progression to AIDS after infection with HIV-1. Here we test the consistency of HLA-B allelic effects on progression to AIDS, heterosexual HIV transmission, and 'set point' viral levels.


METHODS
We used adjusted Cox proportional hazard models in previously published relative hazard values for the effect of HLA-B alleles on progression to AIDS (n = 1089). The transmission study included 303 HIV-1-infected men with hemophilia and their 323 female sex partners (Multicenter Hemophilia Cohort Study cohort). Among 259 HIV-1 seroconverters (Multicenter AIDS Cohort Study cohort), HIV RNA levels at 'set point' were determined in stored plasma samples by a reverse-transcription polymerase chain reaction assay. HLA-B genotyping was performed by sequence-specific oligonucleotide hybridization and DNA sequencing.


RESULTS
Several HLA-B alleles showed consistent associations for AIDS risk, infectivity, and 'set point' HIV RNA. HLA-B*35 was associated with more rapid progression to AIDS (relative hazard 1.39; P = 0.008), greater infectivity (odds ratio 3.14; P = 0.002), and higher HIV RNA (P = 0.01), whereas the presence of either B*27 or B*57 associated with slower progression to AIDS (B*27: relative hazard 0.49, P < 0.001; B*57: relative hazard 0.40, P < 0.0001), less infectivity (odds ratio 0.22 and 0.31, respectively, though not significant), and lower viral levels (P < 0.0001). Importantly, HLA-B polymorphism in female partners was not associated with susceptibility to HIV-1 infection.


CONCLUSIONS
HLA-B polymorphisms that affect the risk of AIDS may also alter HIV-1 infectivity, probably through the common mechanism of viral control, but they do not appear to protect against infection in our cohort.
Gao
Xiaojiang
X
Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
O'Brien
Thomas R
TR
Welzel
Tania M
TM
Marti
Darlene
D
Qi
Ying
Y
Goedert
James J
JJ
Phair
John
J
Pfeiffer
Ruth
R
Carrington
Mary
M
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005060:Europe; D005260:Female; D005838:Genotype; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006467:Hemophilia A / Q000235:genetics / Q000276:immunology* / Q000821:virology; D020010:Heterosexuality; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012747:Sexual Partners; D014481:United States; D019562:Viral Load; D055815:Young Adult
D015235:HLA-B Antigens