Introduction: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
aEpidemiology and Public Health Service, APHP, Hôpital du Kremlin Bicêtre, Université Paris-Sud
bINSERM U1018, Centre for Research in Epidemiology and Population Health, Le Kremlin Bicêtre
cUPMC Univ Paris 06, Laboratory of Immunity and Infection
dINSERM, Laboratory of Immunity and Infection, Paris
eService de Médecine Interne, AP-HP, Hôpital Bicêtre, Univ Paris-Sud 11
fINSERM U1012, Le Kremlin-Bicêtre
gHôpital Pitié Salpêtrière, APHP
hHôpital Necker, APHP, Université Paris Descartes
iUPMC Univ Paris 06
jINSERM, Paris, France.
*Guillemete Antoni, Julien Guergnon, Laurence Meyer and Ioannis Theodorou contributed equally to the writing of this article.
Correspondence to Julien Guergnon, PhD, INSERM, Paris, France. E-mail: firstname.lastname@example.org
Received 26 September, 2012
Revised 4 February, 2013
Accepted 26 February, 2013
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).