AUTHOR=Vos Wilhelm A. J. W. , Groenendijk Albert L. , Blaauw Marc J. T. , van Eekeren Louise E. , Navas Adriana , Cleophas Maartje C. P. , Vadaq Nadira , Matzaraki Vasiliki , dos Santos Jéssica C. , Meeder Elise M. G. , Fröberg Janeri , Weijers Gert , Zhang Yue , Fu Jingyuan , ter Horst Rob , Bock Christoph , Knoll Rainer , Aschenbrenner Anna C. , Schultze Joachim , Vanderkerckhove Linos , Hwandih Talent , Wonderlich Elizabeth R. , Vemula Sai V. , van der Kolk Mike , de Vet Sterre C. P. , Blok Willem L. , Brinkman Kees , Rokx Casper , Schellekens Arnt F. A. , de Mast Quirijn , Joosten Leo A. B. , Berrevoets Marvin A. H. , Stalenhoef Janneke E. , Verbon Annelies , van Lunzen Jan , Netea Mihai G. , van der Ven Andre J. A. M. TITLE=The 2000HIV study: Design, multi-omics methods and participant characteristics JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.982746 DOI=10.3389/fimmu.2022.982746 ISSN=1664-3224 ABSTRACT=Background

Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets.

Methods

The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort.

Results

Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine.

Conclusion

The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.