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HLA-B alleles associate consistently with HIV heterosexual transmission, viral load, and progression to AIDS, but not susceptibility to infection.

May
2011
23

posted by kkaneshi | |

Authors
Gao, Xiaojiang.  O'Brien, Thomas R.  Welzel, Tania M.  Marti, Darlene.
Qi, Ying.  Goedert, James J.  Phair, John.  Pfeiffer, Ruth.  Carrington,
Mary.
Institution
Cancer and Inflammation Program, Laboratory of Experimental Immunology,
SAIC Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
Title
HLA-B alleles associate consistently with HIV heterosexual transmission,
viral load, and progression to AIDS, but not susceptibility to infection.
Source
AIDS.  24(12):1835-40, 2010 Jul 31.
Other ID
Source: NLM. NIHMS213323 [Available on 07/01/11]
Source: NLM. PMC2902625 [Available on 07/01/11]
Abstract
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.

CONCLUSION: 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