Exploring HLA class II allele associations with markers of HIV control

Abstract

Among HIV seropositive individuals, the progression of the HIV-related disease is quite heterogeneous, partially due to the genetic background of the patients. Different host genetic factors have been statistically associated with HIV disease control or progression, especially HLA class I (HLA-I) polymorphisms because of the direct role that these molecules play in the immune response against the virus. In recent years, the immune response against HIV based on CD4+ T helper cells and HLA class II (HLA-II) restricted responses has gained importance to refine current vaccine approaches. Therefore, the main objective of the present study was to explore potential statistical associations of HLA-II with markers of HIV control, in particular HIV viral load and CD4+ counts, in a Peruvian cohort of almost 400 individuals with existing HIV infection or at high risk for infection. Additionally, we also studied the associations of HLA-II with the presence of T cell responses to overlapping peptides (OLPs) covering the whole HIV proteome. In order to achieve such objectives, different statistical approaches using the R statistical software were applied. Mainly, the Fisher’s Exact Test was used to assess whether the expression of certain HLA-II alleles was associated with HIV infection or with the response to the different HIV epitopes. On the other hand, the Mann-Whitney Test was used to detect differences in viral loads or CD4+ counts between patients with or without a certain HLA-II allele. In our analyses, alleles HLA-DRB1*1201 and HLA-DRB1*1302 appeared to be significantly associated (p<0.05) with low and high viral loads, respectively. A number of additional alleles were significantly associated with CD4+ counts. Most of the identified associations included the HLA-DRB1 locus, the most polymorphic of the HLA class II loci. Additionally, expression of HLA-DRB1*1201 was associated with T cell response to OLP 41 in the Gag protein, and HLA-DRB1*1302, with the response to OLP 82 in Nef protein, identifying dominant targets of the T cell response restricted by these two alleles. Overall, the associations of HLA-DRB1*1201 and HLA-DRB1*1302 with viral load, support previous data suggesting a potential effect of the CD4+ T cell responses on HIV disease control.