Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis.

• Main Authors: Daniel T Claiborne, Eileen P Scully, Christine D Palmer, Jessica L Prince, Gladys N Macharia, Jakub Kopycinski, Clive M Michelo, Howard W Wiener, Rachel Parker, Krystelle Nganou-Makamdop, Daniel Douek, Marcus Altfeld, Jill Gilmour, Matt A Price, Jianming Tang, William Kilembe, Susan A Allen, Eric Hunter
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2019-08-01
• Series: PLoS Pathogens
• Online Access: https://doi.org/10.1371/journal.ppat.1007981
• ISSN: 1553-7366; 1553-7374

Despite extensive research on the mechanisms of HLA-mediated immune control of HIV-1 pathogenesis, it is clear that much remains to be discovered, as exemplified by protective HLA alleles like HLA-B*81 which are associated with profound protection from CD4+ T cell decline without robust control of early plasma viremia. Here, we report on additional HLA class I (B*1401, B*57, B*5801, as well as B*81), and HLA class II (DQB1*02 and DRB1*15) alleles that display discordant virological and immunological phenotypes in a Zambian early infection cohort. HLA class I alleles of this nature were also associated with enhanced immune responses to conserved epitopes in Gag. Furthermore, these HLA class I alleles were associated with reduced levels of lipopolysaccharide (LPS) in the plasma during acute infection. Elevated LPS levels measured early in infection predicted accelerated CD4+ T cell decline, as well as immune activation and exhaustion. Taken together, these data suggest novel mechanisms for HLA-mediated immune control of HIV-1 pathogenesis that do not necessarily involve significant control of early viremia and point to microbial translocation as a direct driver of HIV-1 pathogenesis rather than simply a consequence.