Associations of functional human leucocyte antigen class I groups with HIV viral load in a heterogeneous cohort.

Autor:	Zucco AG; PERSIMUNE Center of Excellence, Rigshospitalet., Bennedbæk M; Virus Research and Development Laboratory, Virus and Microbiological Special Diagnostics, Statens Serum Institut., Ekenberg C; PERSIMUNE Center of Excellence, Rigshospitalet., Gabrielaite M; Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark., Leung P; PERSIMUNE Center of Excellence, Rigshospitalet., Polizzotto MN; Clinical Hub for Interventional Research, College of Health and Medicine, The Australian National University, Canberra, Australia., Kan V; George Washington University, Veterans Affairs Medical Center, Washington, DC, USA., Murray DD; PERSIMUNE Center of Excellence, Rigshospitalet., Lundgren JD; PERSIMUNE Center of Excellence, Rigshospitalet., MacPherson CR; PERSIMUNE Center of Excellence, Rigshospitalet.
Jazyk:	angličtina
Zdroj:	AIDS (London, England) [AIDS] 2023 Sep 01; Vol. 37 (11), pp. 1643-1650. Date of Electronic Publication: 2023 Apr 03.
DOI:	10.1097/QAD.0000000000003557
Abstrakt:	Objective: Human leucocyte antigen (HLA) class I alleles are the main host genetic factors involved in controlling HIV-1 viral load (VL). Nevertheless, HLA diversity has proven a significant challenge in association studies. We assessed how accounting for binding affinities of HLA class I alleles to HIV-1 peptides facilitate association testing of HLA with HIV-1 VL in a heterogeneous cohort. Design: Cohort from the Strategic Timing of AntiRetroviral Treatment (START) study. Methods: We imputed HLA class I alleles from host genetic data (2546 HIV+ participants) and sampled immunopeptidomes from 2079 host-paired viral genomes (targeted amplicon sequencing). We predicted HLA class I binding affinities to HIV-1 and unspecific peptides, grouping alleles into functional clusters through consensus clustering. These functional HLA class I clusters were used to test associations with HIV VL. Results: We identified four clades totaling 30 HLA alleles accounting for 11.4% variability in VL. We highlight HLA-B∗57:01 and B∗57:03 as functionally similar but yet overrepresented in distinct ethnic groups, showing when combined a protective association with HIV+ VL (log, β -0.25; adj. P-value < 0.05). We further demonstrate only a slight power reduction when using unspecific immunopeptidomes, facilitating the use of the inferred functional HLA groups in other studies. Conclusion: The outlined computational approach provides a robust and efficient way to incorporate HLA function and peptide diversity, aiding clinical association studies in heterogeneous cohorts. To facilitate access to the proposed methods and results we provide an interactive application for exploring data. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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