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. 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.