Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03591003 |
| Other study ID # |
B076201421922 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 2015 |
| Est. completion date |
June 2022 |
Study information
| Verified date |
August 2021 |
| Source |
Centre Hospitalier Universitaire Saint Pierre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Participating countries: Belgium
Context:
In June 2013, WHO notified that "a single dose of YF vaccine is sufficient to confer
sustained life-long protective immunity against YF disease and that a booster dose is not
necessary". . For HIV infected persons the recommendation was less stringent and the position
paper concluded that hiv infected persons may "hypothetically, benefit from a second dose or
booster dose ".1 Recently, WHO changed the recommendations about a booster dose of YF
vaccine, based on the fact that serum neutralizing antibodies against YF are still at
detectable levels after 20-35 years and probably lifelong in immunocompetent patients.
Unfortunately, data on persistence of Neutralizing antibodies Titers (NT) in
immunocompromised patients are missing and only few studies reported data about HIV-infected
patients. Additional data are needed.
Primary objective:
To assess presence / persistence of Neutralizing Titers (NT) of antibodies after YF
immunization in HIV-infected patients.
Secondary objectives:
1. To identify risk factors for early and late waning of NT after YF immunization
2. To modelize kinetics of NT after YF immunization in different subpopulations of HIV
patients, including population of young HIV patients infected vertically
3. To identify risk factors for absence of seroconversion in the year after YF immunization
4. To compare persistence of NT in HIV patients infected vertically or not vertically
5. To quantify seroconversion rate after YF vaccination Methodology / study design This
study is a single arm, non randomized, cross-sectional, multicenter study in AIDS
Reference Centers from Belgium.
The maximum duration of the study for each patient will be 1 visit, consisting of:
- the screening and inclusion visit (single visit V1) to check the patient eligibility,
sign informed consent, perform the biologic tests necessary for the study and answer the
questionnaire
- whenever possible, an additional serum / plasma sample coming from serabank / plasmabank
will be identified for each patient. This sample must have been taken during the year
following YF immunization.
- data about patient's HIV history has to be extracted from the HIV database or from
patients' file
Estimated enrolment 750 patients + 30 patients infected vertically with HIV Primary outcome
Number of HIV patients with protective YF NT ≥ 1:10 at different timepoints after YF
immunization Secondary outcomes
1. Number of patients with protective YF NT ≥ 1:10 in the year following YF immunization
2. Risk factors (demographics and immunovirological parameters, antiretroviral treatment)
for absence of seroconversion in the year following YF immunization
3. Risk factors (demographics and immunovirological parameters, antiretroviral treatment)
of early waning (before 10 years) of YF NT
4. Risk factors (demographics and immunovirological parameters, antiretroviral treatment)
of late waning (after 10 years) of YF NT Eligibility Inclusion criteria
1. Infection with HIV-1 (vertical transmission or not) 2. Immunization with at least one
injection of YF vaccine (Stamaril®,17D strain Rockefeller, Sanofi Pasteur) with proof of
vaccine administration 3. Informed consent signed prior to any study procedure Exclusion
criteria Inability to give informed consent
Substudies
- Whenever possible, an additional sera or plasma sample from the year following YF
vaccine will be selected and analyzed to assess early seroconversion rate
- Whenever possible, an additional sera or plasma sample from the year before YF vaccine
will be selected and analyzed to assess seroconversion rate
- In CHU Saint-Pierre, an additional cohort of patients infected vertically with HIV will
be selected and will participate to the study
Description:
This study is a multicenter and cross sectional study performed in several ARC (AIDS
Reference Centers) in Belgium and coordinated by CHU Saint-Pierre (Brussels, Belgium).
There is two parts in the study: a prospective part and a retrospective part. There is no
control group in this study. Prospective study Sera / plasma samples of HIV patients
immunized with at least one injection of YF vaccine (Stamaril® ,17D strain Rockefeller,
Sanofi Pasteur) will be collected prospectively during the patient's single Visit. Analysis
of samples will assess persistence of neutralizing antibodies titers (NT) against YF.
Retrospective study Whenever possible, serum or plasma sample will also be collected
retrospectively (from a serum/plasma bank). Retrospective collection of samples must identify
at least one sample per patient taken during the year before YF vaccine and from 30 days to
12 months following YF immunization
The retrospective study has three study timepoints :
Baseline is defined as an available sample during the period 12 months to day 0 before YF
vaccination. Timepoint one is defined as a sample between one month and one year after YF.
In case of several samples, the sample nearest to one month will be chosen. Time point two is
defined as the last available sample. In case the patient would have been re-vaccinated in
the meantime (eg for interval higher than ten years; identied as DateVaccine2), the last
sample before revaccination will be chosen.
Objectives of the retrospective study
1. To assess seroconversion rate during the year following YF immunization
2. To identify risk factors (demographics and immunovirological parameters, antiretroviral
treatment ) for not seroconverting after primary vaccination with YF vaccine Description
of the retrospective study Blood samples from HIV patients are kept, often for several
years, in a sample bank. Depending of YF date of immunization, samples from the year
before and following YF immunization will be identified and analysed. The PRNT technique
will be used to assess presence of YF neutralizing antibodies (Serum or Plasma).
Samples will be centralized in CHU Saint-Pierre after one and two years of study. Assessment
of presence of neutralizing antibodies titers (NT) against YF will be performed by PRNT
(Plaque Reduction Neutralizing Test), which is the current gold standard technique.
After, the samples will be sent to France (Laboratory Cerba, Saint-Ouen l'Aumône) or in
Germany (Berlin) to be analyzed. The surplus of your samples will be destroyed once the
analyses described in this document have been carried out, i.e. in principle in maximum 10
years.
At least one sample will be analysed for each patient. A NT ≥ 1:10 will be considered as
protective against natural YF.
Data that will be collected include demographics, date of HIV diagnosis, nadir CD4 and date,
% CD4, CD38/CD8 (if available), CD4 and CD8 count at time of immunization against YF and at
time of serological analysis, ARV therapy at time of immunization against YF and at time of
serological analysis, plasma HIV RNA at time of immunization against YF and at time of
serological analysis, number of YF vaccines, number of months with potential exposure to YF.
Data will be collected by questionnaire and collected by local investigator, for instance by
extraction from an HIV database. A CRF will then be completed by local investigators and sent
to the data manager in CHU Saint-Pierre.
Vertical transmission substudy The same design is applied to this substudy. The population
study is a population of HIV patients infected vertically, selected in only CHU Saint-Pierre.
Laboratory techniques:
Serological analysis will be performed at Centre for Biological Threats and Special Pathogens
in Berlin, using a plaque reduction neutralization test (PRNT). This technique measures the
neutralizing titers (NT: the highest serum dilution able to induce an 80% plaque reduction in
cells infected by the YF17D strain). An YF virus NT ≥ 1:10 is accepted as a serologic
surrogate marker of clinical protection against natural Yellow Fever.
Sampling and data collection:
Serological analysis will be performed on freezed sera/plasma samples (available from a
serum/plasma bank retrospectively) or on fresh sera samples collected prospectively from HIV
patients followed in different Belgian ARC. Samples will be centralized every year in CHU
Saint-Pierre, Brussels.
Serological analysis will be performed at one timepoint for each patient after YF
immunization to assess persistence of NT. When possible, it must also be performed on a
freezed sample from the year before and following YF vaccine.
The following data will be collected, for instance extracted from HIV database of ARC: age,
gender, mode of HIV contamination, ethnic origin, date of diagnosis of HIV, CD4 count nadir
and date of nadir, history of AIDS, CD38/CD8 (if available), %CD4, CD4 and CD8 count, plasma
HIV RNA at time of immunization against YF and at time of serological analysis, treatment for
HIV at time of immunization against YF and at time of serological analysis, date of start of
antiretroviral therapy.
Date(s) of YF immunization(s) will be checked with help of International Certificate of
Immunization for Yellow Fever of every patient or with a medical note from Travel Clinic.
Potential natural YF exposure will be collected by patient questionnaire. All these data have
to be included in the CRF completed by local investigator(s) then sent to the data manager in
CHU Saint-Pierre.
The duration of the study for each patient is one single visit, consisting of the screening
and inclusion visit (visit V1) to check the patient eligibility and to perform the biologic
tests and exams necessary for the study.
