To identify and quantify the HIV reservoir in T-cell subsets of patients who have been on ART for almost 20 years.
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Aim 1) Identify and quantify the HIV reservoir in T-cell subsets after almost
20 years of effective ART.
* Amount of viral DNA in T-cell subsets.
* Amount of 2-LTR circles in T-cell subsets.
* Amount of intracellular viral RNA in T-cell subsets.
* Amount of extracellular viral RNA in plasma.
Aim 2) Determine the characteristics of the different cell subsets with respect
to immunological markers and viral quasi species.
* Sequencing of viral RNA in plasma.
* Sequencing of viral DNA in T-cell subsets.
* Sequencing of HIV DNA integration sites in T-cell subsets.
* Amount of soluble cell-activation markers in plasma.
* Amount of cell-activation markers in T-cell subsets and other cells such as
CD8+ T-cells, monocytes and NK cells.
Aim 3) Determine the reactivation potential of the latently infected T-cell
subsets.
* Amount of intra- and extracellular viral RNA before and after stimulation of
different CD4+ T-cell subsets by anti-latency compounds.
* Amount of intra- and extracellular cell activation markers before and after
stimulation by anti-latency compounds.
Secondary outcome
Not applicable.
Background summary
Currently available antiretroviral therapy (ART) can successfully suppress HIV
replication. However, HIV can persist as an integrated provirus in latently
infected cells and conventional treatment lacks the ability to clear this
reservoir. This reservoir fuels viral rebound following treatment failure or
interruption and is the major obstacle towards eradication of HIV. The major
cellular HIV reservoir during long-term treatment is the CD4+ T-cell. Recently,
this cell population was found to be highly heterogeneous consisting of several
distinct subsets with specific characteristics that may differentially impact
the long-term in vivo persistence. In the UMC Utrecht, we have a unique cohort
of well-characterized patients who were among the first to initiate effective
ART and who delivered a large blood draw in 2005. It is of major interest to
determine the evolution of the viral reservoir using the data available from
this earlier blood draw and longitudinally investigate in which cell subsets
HIV resides after almost 20 years of effective ART. Knowing where and how HIV
persists in long-term treated patients is pivotal for the development of
strategies aimed at eradicating the latent reservoir and ultimately, HIV cure.
Study objective
To identify and quantify the HIV reservoir in T-cell subsets of patients who
have been on ART for almost 20 years.
Study design
Cohort study with a single blood draw procedure.
Study burden and risks
The intended participants are eight HIV-infected UMC Utrecht patients and part
of the CHEESE cohort. The patients in the CHEESE cohort were among the first
HIV patients in the Netherlands on effective ART (1997), and the intended
subset of eight patients has previously (2005) donated a large blood draw
(METC-04017). At that time-point, after 8 years of effective therapy, HIV DNA
could still be detected in these patients. Now, 10 years later, we would like
to re-approach these patients to donate a large blood draw, which will allow us
to longitudinally assess in more detail if and in which T-cell subsets HIV can
reside. The blood-draw procedure will take place at a designated room at the
outpatient clinic (dagbehandeling). The one-time procedure bears little risk
but discomforts associated with large volume blood draws may occur such as
dizziness, headache, nausea, sweating, hyperventilation, fainting and fatigue.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
The intended participants are eight HIV-infected UMC Utrecht patients and part of the CHEESE cohort. The patients in the CHEESE cohort were among the first HIV patients in the Netherlands on effective ART (1997), and the intended subset of eight patients has previously (2005) donated a large blood draw (METC-04017). At that time-point, after 8 years of effective therapy, HIV DNA could still be detected in these patients. Now, 10 years later, we would like to re-approach these patients to donate a large blood draw, which will allow us to longitudinally assess in more detail if and in which T-cell subsets HIV can reside.
Exclusion criteria
Unability to undergo a large blood draw in the opinion of the treating physician.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL55494.041.16 |