The general objective of this study is to elucidate the cellular components for HIV-1 infection in children.
ID
Source
Brief title
Condition
- Immune disorders NEC
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. CCR5, other chemokine receptor and phenotype expression on cells derived
from cord blood of healthy neonates and cord blood from neonates born to
HIV-1-infected mothers.
2. define chemokine receptor upregulation as well as phenotype alterations in
cells from cord blood by proliferative stimulation via a.o. cytokines (e.g.
IL-2, IL-7).
3. determine productive HIV-1 infection rates in vitro of naïve T cells and
other white blood cells derived from cord blood of healthy neonates and cord
blood from neonates born to HIV-1-infected mothers.
4. Test whether infection (3.) can be inhibited by CCR5 antagonists and
monoclonal antibodies against other chemokines receptors.
5. rate of infection of the above cells isolated from the two sets of cord
blood with HIV-1 strains obtained from HIV-1 infected children.
6. assess the repertoire of co-receptors for HIV-1 infection on CD4+ T cells
and other white blood cells from young patients, i.e. CCR5, CCR2 and CXCR4
expression in the perspective of extensive subset definition of T cells (memory
/ naïve etc)
7. define the genomic form of HIV-1 in the subsequent white blood cells of
HIV-infected infants, e.g. comparing the form of HIV-1 in naïve, memory T cell
subsets as well as blood monocytes.
Secondary outcome
nvt
Background summary
HIV-1 is still spreading rapidly, in particular in young women of childbearing
age. This implies that children are at risk to become infected through maternal
to child transmission (MTCT) of HIV-1 e.g. during pregnancy and delivery.
Interventions to prevent transmission MTCT such as HAART and neonatal ART
prophylaxis have reduced transmission from 25%-40% to less than 1 %. However
there are reports suggesting long term effects of ART exposure regarding
hematological and mitochondrial abnormalities. Thus current prevention
strategies are successful but not ideal. Furthermore the number of HIV-1
infected children is also increasing. At the moment UNAIDS has estimated that
approximately 2.300.000 children are infected with HIV-1. Thus the development
of appropriate and successful treatment regimes for HIV-1 infected children are
very important. A thorough understanding of the mechanisms involved in
HIV-1-infection in children is mandatory to develop new successful strategies
to prevent MTCT of HIV-1 and to increase success rates in the treatment of
HIV-1 infected children. With this study we try to elucidate mechanisms during
early HIV-1 infection in neonates.
The immune system in the newborn is immature, as the lymphocytes have not yet
encountered micro-organisms. This is reflected by the presence of non-activated
naïve T-cells (CD45RA+ CD27+ CCR7+). Encounter of these cells with the cognate
antigen results in a maturation of the immune system with memory T cells
(CD45RO+ CD27+ CCR7-).
HIV-1 is a virus that attacks the immune system by infecting predominantly CD4+
T cells. The virus binds to CD4 and co-receptors on the surface membrane of
CD4+ T cells to enter the cell. Under normal conditions, the obligatory
co-receptor for early HIV-1 entry, i.e. chemokine receptor CCR5, is not
expressed on naive CD4+ T cells present in the neonate. However, neonates or
even a fetus with hardly if any memory CD4+ T cells can become infected with
HIV-1 through maternal-to-child-transmission (MTCT). HIV-1 infection in
neonates also progresses more rapidly than in adults with higher plasma viral
loads. Thus, although low if any numbers of CCR5+ T cells are present, rapid
infection and replication of HIV-1 does occur in newly infected neonates and
infants. The aim of this project is to resolve this paradox.
Study objective
The general objective of this study is to elucidate the cellular components for
HIV-1 infection in children.
Study design
Prospective case *control study. Comparison of immunological parameters in 20
cord blood samples of children born to HIV-1-infected mothers and 20 cord blood
samples of children born to healthy mothers.
Study burden and risks
The cord blood samples of the children born to HIV infected mothers are not an
added burden, because a cord blood sample is always obtained for (a.o. the
antiretroviral drug concentration in the cord blood) the current treatment
protocol for prevention of mother to child transmission of HIV-1.
For the mother and child of the healthy mother it is an extra procedure during
the delivery, however it does not need to interfere with the delivery. The
risks for the new-born are absent
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Healthy subjects: healthy pregnant women and their newborn baby for cord-blood withdrawal.;Patients: HIV-1-infected pregnant women and their newborn baby for cord-blood withdrawal.
Exclusion criteria
Healthy subjects:
1. infected with a (chronic) infection
2. immune system altering disease
3. immune system altering medication;Healthy and HIV-1-infected mothers:
4. preterm delivery at less than 33 weeks
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 | NL14795.018.06 |