Ex vivo activation characterization and targeting of the latent HIV infected reservoir to cure HIV

Combined antiretroviral therapy (c-ART) effectively controls viral replication
but does not affect cells in which the human immunodeficiency virus (HIV) is
latently present. c-ART is not curative, therefore, and is a lifelong therapy.
Finding a way to eradicate HIV from the pool of HIV infected resting memory
CD4+T cells could lead to a definitive cure for HIV, as these cells harbour
replication competent, transcriptionally latent HIV virus.

Recent research has given new insight in mechanisms to purge HIV from the body.
In the light of these findings we identified and tested new compounds that
could stimulate HIV genome expression in a preclinical-clinical drug pipeline.
Identifying potent activators of HIV transcription in vitro could help reaching
an optimal medical solution towards HIV latency.

1. Ex vivo stimulation of HIV genome expression in latently infected peripheral
blood mononuclear cells (PBMC's) from patients on cART using new and
established compounds.
2. To characterize latently HIV-1 infected peripheral blood mononuclear cells
(PBMC*s) ex vivo before and after addition of new and established compounds
(alone and in combination).
3. To characterize potential predictive biomarkers of the size of the latent
HIV-1 reservoir.
4. Setup prospective cohort for HIV cure research.

This is an invasive observational research with no intervention on patients. In
vitro experiments are performed on patient derived material.

The potential risk of participation in this study is the development of an
adverse reaction on the blood obtainment. In the leukapheresis procedure, two
2.5 cm venous catheters will be inserted in the patient*s elbows (one in each)
to drain whole blood to the leukapheresis machine. This is a well-defined
routine procedure performed by highly skilled personnel and which takes some
3-5 hours. In short, the machine will isolate peripheral blood mononuclear
cells from blood based on weight and granularity. Erythrocyte and plasma
fraction will be given back to the patient. The main adverse reactions related
to leukapheresis are haematomas, a slight increased risk on infection (e.g.
flebitis) and vasovagal complaints or collaps. The leukapheresis procedure
might cause a slight decrease in total erythrocytes due to cell lysis in the
machine. Although the occurrence of leukapheresis induced anaemia is unlikely,
we will exclude patients with pre-existent anaemia. The risks associated with
standard phlebotomy are minimal. The follow up phlebotomies or leucapheresis
will be done during routine follow up and routine blood sampling for a maximum
of 4 years. No extra visits are required. The maximum amount of blood is equal
to the amount that can be drawn at 1 standard blood donation (500mL) and the
total amount stays well below the acceptable amount by the blood bank over this
4 year period.