Human leukocyte antigen (HLA) class I-driven long-term protection against HIV-1 is mainly associated with HLA-B∗27 and HLA-B∗57. This effect is observed early after infection. Clarification needs to be established concerning the moment of action for the other HLA-B or HLA-C alleles.
HLA-B and HLA-C alleles from 111 individuals that control HIV-1 disease for over 8 years and from 747 seroconverters frequencies were compared. Also, HLA-B and HLA-C influence on early levels of plasma HIV-RNA, cellular HIV-DNA, CD4, CD8 and CD4/CD8 ratio was evaluated among the seroconverters. We performed univariate, multivariate and haplotypic analyses in order to disentangle the respective contribution of the HLA-B and HLA-C genes.
The haplotypes analysis shows three patterns of protective effects of HLA-B and HLA-C alleles or haplotypes. First, the HLA B∗57, HLA-B∗27, HLA-B∗13 and HLA-C∗14 alleles, which have a strong effect on long-term disease control, also influence at least one of the early infection phenotypes. Second, HLA-B∗52 has a strong effect during early time points on HIV-RNA without significant effect on the long-term control of HIV-1. Finally, the HLA-B∗14-C∗08 haplotype has a strong effect on the long-term protection, without influencing early viral control.
Our study highlighted independent effects of HLA-B and HLA-C alleles on HIV-disease progression. Furthermore, some alleles appeared to be specifically associated with either long-term control or early virological parameters, suggesting different immunological mechanisms according to the disease stages.