The primary objective of the NOVA study is the establishment of a prospective cohort study of patients that initiate cART during the acute infection phase. The secondary objective is to characterize the viro-immunological factors that correlate with…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- the cell associated viral reservoir size (total integrated HIV DNA, 2LTR
circles, single copy RNA, cell associated RNA, viral outgrowth and inducible
RNA) in peripheral blood, lymph node and GALT and viral load in CSF during the
three to five years after initiation of cART.
- the functional properties of the HIV-specific CD8+ T cell, B cell and T
follicular helper cell response during the three years after initiation of cART.
- immune activation parameters (type I interferons, IFN*, IL-6, IL-10, IL-15,
IL18, IL-22, sCD14, CRP, TGF*, IL-1, IL8, sCD163, IP-10) during the three years
after initiation of cART.
Secondary outcome
- the replication competent viral reservoir (as described in methods section,
paragraph 8.3.2) in peripheral blood, lymph nodes, GALT and CSF during the
three years after initiation of cART.
Background summary
There is renewed interest in finding a cure for HIV infection. Recent studies
show that in a select group of individuals the initiation of combination
anti-retoviral therapy (cART) during the early phase of infection results in
long-term absence of viremia following treatment interruption after prolonged
treatment. These patients are described as having achieved a *post-treatment
viral remission*. It is unclear why this is only seen in a subset of
individuals. However, an important factor associated with post-treatment viral
control appears to be the early limitation of viral reservoir formation. There
are many unsolved issues regarding the question which virological and
immunological factors determine which individuals achieve a *post-treatment
viral remission*. First studies suggest that the early reduction of viral
reservoir size and potential accompanying preservation of immune function may
be important factors. Furthermore, patients that initiate cART during acute
infection are potential candidates for additional therapeutic strategies, such
as latency reversing agents (LRAs) or therapeutic vaccination.
Study objective
The primary objective of the NOVA study is the establishment of a prospective
cohort study of patients that initiate cART during the acute infection phase.
The secondary objective is to characterize the viro-immunological factors that
correlate with achievement of *post-treatment viral remission* for several
years in these patients.
Study design
Prospective cohort study. Patients diagnosed with an acute HIV infection (AHI)
are offered immediate standard first-line cART. In consenting patients, at
several time points samples will be obtained to analyze the size and
characteristics of the viral reservoir and the accompanying immune function.
Three groups are assembled based on the preparedness of individual patients to
participate in the extensiveness of sampling. Patients that accept early
treatment and follow-up but decline additional blood and tissue sampling (lymph
node, GALT and cerebral spinal fluid (CSF)) are included in group 1
(*standard*) and only routine diagnostic procedures are performed. Patients
willing to undergo, in addition to routine monitoring, leukapheresis and blood
sampling for PBMC and virological analyses are included in group 2 (*less-
invasive*). In group 3 (*extended*) additional tissue and CSF sampling will be
performed for the proposed viro-immunological analyses.
This set up allows to guide the duration of cART based on
viro-immunological parameters and to adjust cART in case better cART strategies
may become available in future. Furthermore, based on the available data that
show preservation of immunity and reduction in viral reservoir size, the AHI
patients that start therapy early may have better responses to future cure
strategies such as therapeutic vaccination or LRAs.
Study burden and risks
Offering treatment in early HIV infection is currently recommended in clinical
guidelines for treatment of HIV infection. This recommendation is based on
studies showing improvement of markers of disease progression, decrease of
severity of acute disease, lowering of the viral setpoint (associated with
disease progression) and a reduction in size of the viral reservoir. The burden
and risks associated with study participation are related to tissue sampling:
lymph node excision biopsy, sigmoid biopsies, lumbar puncture at three and
leukapheresis at two timepoints during the study (week 0 (baseline), week 24
and week 156 (3 years)). The risks of sampling are considered minimal (see also
section on *sampling*). These study procedures are necessary to answer the
question underlying the research proposal that aim to characterize the
determinants of "post-treatment viral control", under which the most important
are the immune response and viral reservoir in blood, lymph node, gut
associated tissue and cerebral spinal fluid. In order to minimize burden
associated with study visits, we aim to combine visits for routine clinical
care with routine clinical visits.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet the
following criteria:
-Written informed consent to store samples and perform genetic testing.
-Separate written informed consent for invasive sampling procedures:
leukapheresis, sigmoidoscopy with biopsies, lymph node biopsy or excision
biopsy and lumbar puncture, to store samples and perform genetic testing. - Age
>= 18 years
- An acute HIV-1 infection, defined according to the modified Fiebig stages
I-IV, as described in the previous paragraph (HIV-1 RNA positive and 4th
generation ELISA negative or HIV-1 RNA positive and 4th generation HIV ELISA
positive with indeterminate Western Blot). Patients in Fiebig stage V and VI
will only be included if they have a documented negative HIV test 6 months
prior to the (first) positive test.
-Female subjects should be willing to use adequate contraception.
Chronic control group:
-Written informed consent to store samples and perform genetic testing
-Separate written informed consent for sampling procedure: leukapheresis (or
large blood draw), and/or lymph node excision biopsy, with storage of samples
-Age >= 18 years
-ART initiated in the chronic infection phase and chronic HIV-infection as
confirmed by Western Blot (p31 positive)
-Three to 5 years on ART with undetectable viral load and no more than two
consecutive blips of >100 HIV RNA copies per mL of plasma in the year before
enrollment
Elite control group:
-Written informed consent to store samples and perform genetic testing
-Separate written informed consent for sampling procedure: leukapheresis (or
large blood draw), and/or lymph node excision biopsy, with storage of samples
-Age >= 18 years
-Natural control of HIV infection, defined as having 3 undetectable HIV-1 RNA
measurements >12 months upon diagnosis or 90% of HIV-1 RNA measurements
undetectable >10 years.
Exclusion criteria
-Contraindication for proposed cART regimen (e.g. impaired renal function) for
participants enrolled with an acute HIV infection
-Mental disorder that in the view of the investigator would interfere with
adherence to the treatment or the study procedures, or the decision to
participate in the study.
-Immunosuppressive medication or other diseases associated with
immunodeficiency.
Design
Recruitment
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
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 | NCT05728996 |
| CCMO | NL51613.018.14 |