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The 2000HIV study: Design, multi-omics methods and participant characteristics.
Wilhelm A J W Vos1,2, Albert L Groenendijk1,3, Marc J T Blaauw1,4
1Department of Internal Medicine and Infectious Diseases, Radboudumc, Radboud University, Nijmegen, Netherlands.
Frontiers in Immunology
|January 6, 2023
Summary
The 2000HIV study uses multi-omics to understand immune dysregulation in people living with HIV (PLHIV) on combination antiretroviral therapy (cART). This research aims to find new biomarkers and drug targets for better HIV treatment and potential cure.
Area of Science:
- Immunology
- Genomics
- Virology
- Public Health
Background:
- People living with HIV (PLHIV) on long-term combination antiretroviral therapy (cART) exhibit persistent immune activation, accelerated aging, and increased non-AIDS comorbidities.
- Understanding the underlying molecular pathways is crucial for improving health outcomes in PLHIV.
Purpose of the Study:
- To apply a multi-omics approach to a large cohort of PLHIV to identify novel biomarkers and genetically validated therapeutic targets.
- To unravel the biological pathways contributing to immune dysregulation, non-AIDS comorbidities, and the latent viral reservoir in PLHIV.
Main Methods:
- The 2000HIV study is a prospective longitudinal cohort including PLHIV on cART and untreated HIV spontaneous controllers.
- In-depth multi-omics characterization (genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics), immunological assays, immunophenotyping, and latent viral reservoir assessment.
- Clinical measurements include cardiovascular assessments, hepatic steatosis/fibrosis evaluation, psychological assessments, and COVID-19 history/vaccination status.
Main Results:
- The study enrolled 1895 PLHIV across discovery (1559) and validation (336) cohorts, representative of Western European HIV populations.
- Included diverse demographics (28.8% cis-women, 24.4% non-whites, 71.8% MSM) and extreme phenotypes (spontaneous controllers, rapid progressors, immunological non-responders).
- Identified individuals with high cardiovascular risk (>20% 10-year risk), documented COVID-19 infections (12.3%), and vaccination rates (25.0%).
Conclusions:
- The 2000HIV study established a comprehensive multi-omics dataset for PLHIV to discover new biological pathways and biomarkers.
- Findings aim to elucidate non-AIDS comorbidities, extreme phenotypes, and the latent viral reservoir impacting PLHIV health.
- The ultimate goal is to advance personalized care strategies and contribute to a potential cure for HIV.
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