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HIV

The HIV group focuses on the virus-host interactions that determine the pathogenesis of this chronic infection. Viral factors are addressed by next generation sequencing, in combination with virus replication kinetics studies and functional assays of individual genetic elements.

figuur1 HIV
Figure 1:Expression of part of the DCTRN vaccine (Rev-GFP) in the nucleus of transfected cells in the laboratory.
The fluorescent signal comes from the GFP part of the protein. This is not included in the vaccine

The host part is studied with assays for specific immune responses against HIV, in combination mRNA profiling of PBMC from HIV-infected patients. Manipulation of these interactions towards a favorable equilibrium for the host is undertaken in immunotherapy trials. One trial (DCTRN vaccination trial) in collaboration with the Vrije Universtiteit Brussel (VUB) has already been completed and analyzed in great detail. 

A new therapeutic vaccination trial in HIV-infected patients is currently being prepared: iHIVARNA. This phase II trial will be performed in collaboration with two partners in Belgium and two partners in Spain.

ongoing research projects:

  • Therapeutic vaccination trials in HIV infection
  • HIV functional cure, what can be learned from HIV-2 infection?


Therapeutic vaccination trials in HIV infection


Research team:

Rob Gruters (PhD)
Wesley de Jong (MD, MSc)
Patrick Boers (BSc)


Selection of publications:


HIV functional cure, what can be learned from HIV-2 infection?
 
 

Research team:

Rob Gruters (PhD)
Patrick Boers (BSc)
Cynthia Lungu (BSc) 


Publications:

figuur 2 HIV
Figure 2: Set up of the DCTRN approach. After inclusion in the study blood is obtained from the participant. Peripheral Blood Mononuclear Cells (PBMC) are isolated. In the laboratory monocytes (M) are separated from the rest of the PBMC en cultured in vitro. They differentiate into Dendritic Cells (DC). The DC are then matured into mDC. After loading with mRNA's encoding the three HIV immunogens Tat, Rev and Nef, the mRC are injected in the same patient (autologous vaccination).

figuur 3 HIV
Figure 3: Scheme of the trial time line. After inclusion blood is obtained via leukapheresis and the autologous vaccine is prepared. The patients receive four autologous vaccinations, with four-week intervals. Two weeks after the last vaccination, treatment is interrupted. At four time points extra blood is taken to monitor the effect of vaccination on the immune responses against HIV.

figuur 4 HIV
Figure 4: Principal Component Analysis (PCA) of the blood transcriptome. The mRNA expression of PBMC was monitored with Affymetrix gene hybridization chips. This measures all RNA's that are expressed. In the figure it is seen that HIV-infected patients (PreVac) cluster together but differently from healthy controls (HC). After vaccination there is a major shift in the mRNA expression profile, which lasts for at least 40 weeks. Analysis of the profile indicates that there is a T cell immune response after vaccination.


News about HIV and the department

PrEP is cost effective as a prevention pill
The HIV prevention pill PrEP can prevent between 1,000 and 2,500 new HIV infections over the coming ten years. Furthermore, preventive use of this pill, which is a combination of the antiretroviral drugs tenofovir and emtricitabine, is cost effective. This has been shown by researchers from Erasmus MC and AMC, who September 2016 published their findings in the leading scientific journal Lancet Infectious Diseases.

Article in the Lancet Infectious Diseases
Read the newsitem in our newssection: PrEP is cost effective as a prevention pill