"Persistence of Neutralizing Antibodies Against Yellow Fever (YF) in HIV-infected Patients"

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

• To assess seroconversion rate during the year following YF immunization
• 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.

Inclusion criteria

• Infection with HIV-1 (vertically infected or not)
• Immunization with at least one injection of YF vaccine (Stamaril®,17D strain Rockefeller, Sanofi Pasteur) with proof of immunization
• Informed consent signed prior to any study procedure (for the Prospective part of the study )

Exclusion criteria

• Inability to give informed consent or incapacitation (for the Prospective part of the study)