A metagenome-wide association study of HIV disease progression in HIV controllers. Â Â iScience
Some HIV controllers experience immunologic progression with CD4+ T cell decline. In this study, Real et al. aimed to identify genetic factors associated with CD4+ T cell lost in HIV controllers.
Non-long-term non-progressor HIV phenotype was defined as CD4+ T-cells
A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No single nucleotide polymorphism (SNP) or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual Genome-wide association studies (GWAS) or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]),nMICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p =0.017; OR=1.39]) showed nominal association with this phenotype.
In conclusion, this study performed the first meta-GWAS focusing in the long-term maintenance of CD4+ T cells in HIV controllers. These results suggest that genetic factors previously associated with the overall HIV controller phenotype, mainly those linked to PSORS1C1, HLAB, and MICA loci, seem to have a role in this complex trait. The results of the present study could help to refine the best definition for HIV controllers. Consequently, these HIV controllers should be considered as the best model of functional cure. The study of this specific phenotype could help to design new strategies for preventing HIV progression, not necessarily associated with antiretroviral treatment, in those subjects who show CD4+ T cell loss.