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2. The 2000HIV study:Design, multi-omics methods and participant characteristics

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., 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., and van der Ven, Andre J.A.M.

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

Published
2022

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