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Review of "Gene Dysregulation among Virally Suppressed People Living with HIV Links to Non-AIDS Defining Cancer Pathways"

Reviewers: J Nemeth (Universitätsspital Zürich) | 📒📒📒 ◻️◻️

Published onJun 30, 2024
Review of "Gene Dysregulation among Virally Suppressed People Living with HIV Links to Non-AIDS Defining Cancer Pathways"
key-enterThis Pub is a Review of
Gene dysregulation among virally suppressed people living with HIV links to non-AIDS defining cancer pathways
Gene dysregulation among virally suppressed people living with HIV links to non-AIDS defining cancer pathways
Description

Abstract Combination antiretroviral therapy (ART) has changed the landscape of the HIV epidemic by providing an effective means for viral suppression to people living with HIV (PLWH). Understanding living with HIV as a chronic disease requires an improved understanding of how HIV and/or ART impacts susceptibility to and development of co-occurring conditions. Genome-wide gene expression (transcriptome) differences provide a key view into biological dysregulation associated with living with HIV. Here we present the first whole blood transcriptome-wide study comparing gene expression profiles between virally suppressed PLWH and HIV negative individuals (N=555). We identify 566 genes and 5 immune cell types with differential proportions by HIV status, which were significantly enriched for immune function and cancer pathways. Leveraging quantitative trait loci (QTL) for these HIV status-associated genes, partitioned heritability, and colocalization analyses, we observed limited genetic drivers of these relationships. Our findings suggest that gene dysregulation does not return to a pre-infection state for virally suppressed PLWH, and that persistent gene dysregulation is broadly associated with immune function and cancer pathways, highlighting potential biological drivers for these causes of excess mortality and targets for pharmacological preventative treatment among PLWH.

To read the original manuscript, click the link above.

Summary of Reviews: The study compares gene expression profiles in whole blood between people living with HIV (PLWH) on antiretroviral therapy (ART) and non-HIV individuals and identified persistent gene dysregulation in PLWH despite viral suppression. The reviewer points out several limitations, including the constraints of whole-blood transcriptomics, the absence of clinical phenotyping, and the relevance of integrating heritability data to "inflammatory" diseases. Overall, the reviewer advises a cautious interpretation of the findings' biological and clinical relevance. 

Reviewer 1 (Johannes N…) | 📒📒📒 ◻️◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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