Primary objectives: 1. To develop a prospective cohort in the Netherlands of chronic HIV infected patients with in-depth reservoir characterization for future cure interventions.2. To study the evolution of the HIV reservoir and immune host…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. The evolution in reservoir size ex vivo as assessed as the number of cells
expressing viral RNA and viral protein Gag (vRNA/prGag +/+) in HIV patients on
cART at week 24 and 48 after treatment initiation.
Secondary outcome
1. The evolution in reservoir size ex vivo as assessed as the number of cells
expressing viral RNA and viral protein Gag (vRNA/prGag +/+) in HIV patients on
cART at week 24, 48 and 156, and later, after treatment initiation.
2. The evolution of cytotoxic T-lymphocyte responses and inflammatory
environment (cell subpopulations, phenotypical cell characterization,
pro-inflammatory cytokines), and its relation to the reservoir (endpoint 1.1
and 2.1) and viral load setpoints pre-cART.
3. Assessment of additive, synergistic, or antagonistic effects of
(combinations of) established and novel LRA ex vivo as determined by increase
in cellular HIV-RNA, protein production and cell decay.
4. Assessment of the underlying mechanisms to explain observed differences in
reservoir size and LRA effects, e.g. chromatin accessibility, transcription
factor binding, HIV promotor sequencing, or transcriptomics.
5. Differences in the reservoir size and activity, and immune responses (immune
activation, cytokines, T/B/NK cell phenotype and functionality) between the HIV
subtypes.
6. Evaluation of clinical parameters with reservoir size, activity and host
immune responses, including sex, ethnicity, INSTI pharmacokinetics, and HIV
clinical characteristics (CD4+T-cell and HIVRNA pre-cART, comedication, HIV
center for disease control (CDC) A/B/C events)
7. Correlation between established and future assays of the reservoir*s size
and activity.
Background summary
HIV cannot be cured with the current treatment armamentarium. A reservoir of
latently HIV infected long lived CD4+T-cells is present in patients with HIV
that are not affected by antiretroviral therapy. The evolution of this
reservoir after therapy initiation is ill understood, as are the potential
strategies to eradicate this reservoir. This study aims to anticipate on future
HIV cure strategies by building a cohort to study ex vivo the reservoirs of HIV
patients, the obstacles to cure HIV, and new therapeutic compounds and
strategies.
Study objective
Primary objectives:
1. To develop a prospective cohort in the Netherlands of chronic HIV infected
patients with in-depth reservoir characterization for future cure interventions.
2. To study the evolution of the HIV reservoir and immune host responses over
time during antiretroviral therapy.
Secondary objectives:
1. To explore established and putative new interventions aimed at curing HIV.
2. To explore differences in reservoir size, activity and host responses, and
their relation with clinical characteristics, between patients with different
dominant HIV subtypes and sexes.
3. To compare and validate new reservoir assays with current established
assays.
Study design
Prospective non-interventional cohort study
Study burden and risks
There are no expected benefits for participants in this study. A potential
future benefit can be that insights from this study can provide an advantageous
position to participate in future cure intervention studies where the kind of
measurements done in this study are very likely necessary to take into account
for participation. The potential risk of participation in this study is the
development of an adverse reaction on the blood obtainment. The main adverse
reactions related to leukapheresis are haematomas, a slight increased risk on
infection (e.g. flebitis) and vasovagal complaints or collapse. 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 symptomatic
anaemia as stated in the exclusion criteria and hemoglobulin levels are
routinely monitored during the procedure. The patients will be able to contact
the investigators if any AE will occur. Another risk is that unexpected results
occur from routine lab measurements, e.g. sex hormones, that warrant work-up.
As internists who treat the patients, we are trained and proficient in the
work-up and treatment of laboratory abnormalities of the measured variables,
including hormonal disturbances that are measured for the aim of this study. In
case of exceptional findings, internist-endocrinologist are direct colleagues
within the internal medicine section and there is a 24/7 consultant
internist-endocrinologist on call who can immediately be reached by the
internist-infectious diseases specialists should the clinical profile or
laboratory results necessitate this. The study cannot be done with another
group since participants need to be infected with HIV and have a medical
indication to start cART.
Wytemaweg 80
Rotterdam 3015CE
NL
Wytemaweg 80
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
Adult chronic HIV infected patients of >=18 years of age who initiate
antiretroviral therapy in routine care.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
1. Inability to place venous catheters to draw blood.
2. Major comorbidities:
a. Severe symptomatic anemia or recent symptomatic cardiovascular event
(unstable angina pectoris, decompensated heart failure, myocardial infarction).
b. The inability to participate due to any other relevant social,
environmental, psychological, factors or according to the HIV treating
physician*s judgement.
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 |
|---|---|
| ClinicalTrials.gov | NCT04888754 |
| CCMO | NL72765.078.20 |