2000 HIV Human Functional Genomics Partnership Program (2000-HIV Study)

Primary Objectives

• Employ a systems biology approach to identify a set of candidate biomarkers (BM) in circulation and/or pathways & mechanisms that correlate with particular non-AIDS defining comorbidities (ie NAFLD, CVD) in HIV+ individuals relative to healthy controls; candidate BMs may be single or algorithm-based multi-parameter BM profile.
• Integrate diverse ‘omics’ data to delineate biological processes (biomarkers, pathways, and/or mechanisms) associated with extreme HIV+ clinical phenotypes such as elite controllers, post-treatment controllers, immunological non-responders and rapid progressors.
• Prioritize therapeutic host targets of interest either for drug discovery to identify novel assets (ie screening and/or lead optimization) or for repurposing of clinical phase assets from other disease areas for HIV.

Secondary Objectives

• Evaluate potential relationship of host/immune profiles on efficacy, safety, and tolerability of different standard of care regimens.
• Evaluate the contribution of aging, female gender, and genetic background in host-immune profiles that are: 
  • distinct to HIV infection relative to well-matched healthy controls
  • associated with non-AIDS defining comorbidities (ie SMART Study endpoints amongst others) in HIV infection relative to non-HIV chronic disease.

In 2000 patients with HIV infection who are treated

1. Metadata will be collected from all the participants using standard questionnaires on lifestyle, health and clinical symptoms, including neuropsychiatric symptoms. These questionnaires will be coded with full respect for the privacy of the individuals, will be anonymous, and will not permit the identification of the individuals. Relevant data will also be collected from the patients records, such as medication history, CD4 levels at presentation and follow-up and clinical events.
2. Co-pathology will be assesed:
   • cardiovascular risk scores (D:A:D risk score and Framingham CVD score) will be collected as well as Intima Media Thickness (IMT).
   • Non-Alcoholic Fatty Liver Disease (NAFLD) assessment through specific ultrasound and fibroscan.
3. Blood will be drawn (89 ml) for
   • DNA will be isolated for genetic analysis.
   • The function of the immune system will be analyzed at several levels using circulating cells from venous blood: immunophenotyping will be done using FACS analysis, circulating factors will be measured in plasma or serum, in-vitro stimulations of cells and analysis of mRNA and cytokine responses.
   • Metabolism will be analysed by metabolome analysis.
   • Virological analysis, characterizing the HIV reservoir, HIV resistance and viral sequences in circulating DNA and RNA.
4. Microbiome analysis will be performed on stool, oral, nasal, vaginal, and skin samples.

Internal collaborations

• Erasmus MC HIV Eradication Group (EHEG)

External collaborations

• RadboudUMC
• University Medical Centre Groningen and University of Groningen
• Onze Lieve Vrouwe Gasthuis, Department of Internal Medicin
• Elizabeth-TweeSteden Ziekenhuis, Department of Internal Medicin
• ViiV Healthcare

Prof Dr Annelies Verbon
a.verbon@erasmusmc.nl

Drs. Albert Groenendijk
a.groenendijk@erasmusmc.nl