HLA-Associated Variation in HIV Viral Load in a South American Native Community with Limited HLA Diversity

D.C. MÓNACO ; M. QUIPILDOR; A DI PAOLO; R. COLOCCINI; G. THEILER; M. PANDO; L. FAINBOIM; E. HUNTER; H. SALOMON; D. DILERNIA

Barcelona

Congreso; AIDS Vaccine 2013; 2013

Global HIV Vaccine Enterprise

Background: Pathogen-driven balancing selection has been proposed as an explanation for the high diversity of the HLA system. Different HLA alleles have been associated with variations in HIV viral load. Our aim was to determine the HLA-A and -B diversity in a South American native HIV-positive community and their association with clinical markers of disease progression. Methods: We developed and validated a sequence-based technique for high resolution typing of HLA-A and ?B genes. This technique was implemented to determine the diversity of these genes in a group of 65 HIV-positive native individuals from Oran, Argentina. The comparison between the patient?s HLA alleles and the HIV viral load was made by Mann-Whitney test and the False-Discovery Rate approach was applied to correct for multiple comparisons. Results: The HLA profile of the population under study was consistent with that observed for other native communities from South America. HLA-A diversity was restricted at both group (Heterozygosity Index (H)=0.791) and subtype (H=0.841) level. Alleles A*02:01:01:01, A*24:02:01 and A*31:01:02 accounted for the 83.4% of the genetic frequency. HLA-B diversity was found to be restricted at the group level (H=0.870) but highly diverse at the subtype level (H=0.969). The analysis of the viral load in each HLA allele group showed that HLA-B*35Px-positive patients exhibit significantly higher viral loads (p=0.038, q=0.17) while HLA-B*39- positive patients exhibit significantly lower viral loads (p=0.014, q=0.13) than the negative counterparts. Conclusion: The HLA profile of the HIV-positive native community of Oran showed to be restricted except at the subtype-level in HLA-B, consistent with the high prevalence of endemic infectious diseases in the area. In particular, B*39 is a native allele that mediates a novel association with a better control of the HIV infection.