Systematic screening of viral and human genetic variation identifies antiretroviral resistance and immune escape link.

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Date

1 juin 2021

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Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.67388

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/34061023

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/2050-084X

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_CDF338C143A76

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Serveur Académique Lausannois

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Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/

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Anti-Retroviral Agents/therapeutic use; Cross-Sectional Studies; Drug Resistance, Viral/genetics; Drug Resistance, Viral/immunology; Female; Genome, Human; Genome, Viral; HIV Infections/drug therapy; HIV Infections/genetics; HIV Infections/immunology; HIV Infections/mortality; HLA Antigens/genetics; HLA Antigens/immunology; Humans; Longitudinal Studies; Male; Middle Aged; Mutation; Mutation Rate; Prospective Studies; Risk Assessment; Risk Factors; Switzerland; T-Lymphocytes, Cytotoxic/immunology; Treatment Outcome; HIV; HLA; epidemiology; global health; human; infectious disease; microbiology; mutations

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Therapy Survival skills Survival after airplane accidents, shipwrecks, etc

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H. Nguyen et al., « Systematic screening of viral and human genetic variation identifies antiretroviral resistance and immune escape link. », Serveur académique Lausannois, ID : 10.7554/eLife.67388

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Considering the remaining threat of drug-resistantmutations (DRMs) to antiretroviral treatment (ART) efficacy, we investigated how the selective pressure of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes drives certain DRMs' emergence and retention. We systematically screened DRM:HLA class I allele combinations in 3997 ART-naïve Swiss HIV Cohort Study (SHCS) patients. For each pair, a logistic regression model preliminarily tested for an association with the DRM as the outcome. The three HLA:DRM pairs remaining after multiple testing adjustment were analyzed in three ways: cross-sectional logistic regression models to determine any HLA/infection time interaction, survival analyses to examine if HLA type correlated with developing specific DRMs, and via NetMHCpan to find epitope binding evidence of immune escape. Only one pair, RT-E138:HLA-B18, exhibited a significant interaction between infection duration and HLA. The survival analyses predicted two pairs with an increased hazard of developing DRMs: RT-E138:HLA-B18 and RT-V179:HLA-B35. RT-E138:HLA-B18 exhibited the greatest significance in both analyses (interaction term odds ratio [OR] 1.169 [95% confidence interval (CI) 1.075-1.273]; p-value

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