Vaccination Response in ImmunoCompromised Host. Immune Response After Vaccination Against Pandemic A/H1N1 Influenza
Vaccination Response in ImmunoCompromised Host. Immune Response After Vaccination Against Pandemic A/H1N1 Influenza
As recommended by the Dutch Health Council, certain risk groups and health care workers in
 The Netherlands were vaccinated to prevent morbidity due to pandemic influenza A/H1N1. Adults
 were vaccinated twice with the monovalent influenza A/California/2009(H1N1) MF59-adjuvanted
 surface-antigen vaccine Focetria® (Novartis). The vaccination campaign was executed by
 general practitioners.

 The aim of the study is to verify whether HIV-infected individuals generate an adequate
 immune response after the first and after the second vaccination.
AIM OF THIS STUDY:

 Primary objective: Do HIV-infected individuals mount a protective humoral response following
 vaccination for pandemic influenza A/H1N1 with the monovalent influenza
 A/California/2009(H1N1) MF59-adjuvanted surface-antigen vaccine Focetria® (Novartis).

 Secondary objective: 1) To evaluate the strength of the immune response in HIV-infected
 individuals compared to healthy volunteers. 2) To evaluate whether a second dose,
 administered at least 21 days after the first increases the proportion of HIV-infected
 individuals that have a titer above the threshold associated with protection. 3) To assess
 whether vaccination is associated with an increases in HIV-replication. 4) To assess whether
 very early antibody responses occur, which may may indicate immunological memory, for example
 due to cross reactivity from past influenza infection or vaccination.

 STUDY DESIGN:

 This is not an interventional study. In this single-centre observational study we will
 monitor the immune response in a cohort of people who are to be vaccinated during the
 national vaccination campaign.

 Population: The population base for this study consists of HIV-infected adult outpatients at
 our hospital and of healthy hospital employees. All Dutch and English speaking HIV-infected
 LUMC outpatients above 18 years of age, on a stable antiretroviral regimen or not yet in need
 of treatment, are sent a letter inviting them to take part. Healthy hospital employees are
 invited to take part with a letter, which is handed out upon vaccination. Inclusion is
 possible until three days after the first vaccination. Exclusion criteria are: use of
 systemic immunosuppressive medication, an ongoing infection, recent flu-like symptoms and
 pregnancy. The following characteristics are documented at baseline: age, gender,
 co-morbidity, medication, year of prior influenza vaccinations and year of diagnosis of HIV
 infection. All participants are requested to fill out standardized diary assessing flu-like
 symptoms and use of new medication during the 60 day follow-up.

 Laboratory analysis: Lymphocyte counts are determined at baseline, prior to vaccination. A
 serum sample is taken prior to the first vaccination (day -30 to day 0), prior to the second
 vaccination (day 17-20) and after the second vaccination (day 60). Viral load is determined
 at baseline (day -30 to day 0) and after the second vaccination (day 5-7) in a subgroup of 10
 persons with undetectable viral load at the preceding outpatient visit. Antibody responses
 are detected in duplicate for each sample by means of hemagglutination-inhibition (HI) assays
 according to standard methods at the Erasmus Medical Center in Rotterdam.

 Statistical analysis: No formal sample-size calculation was performed. We intend to include a
 maximum of 100 subjects with HIV and 50 healthy hospital employees. The crude outcome
 estimates will be adjusted for variables that may influence the outcome (age, CD4 lymphocyte
 count, use of HAART, viral load).
Inclusion Criteria:

 -  Above 18 years of age

 -  Stable antiretroviral regimen or not yet in need of treatment (in case of HIV-infected
 patients)

 Exclusion Criteria:

 -  Use of systemic immunosuppressive medication

 -  An ongoing infection

 -  Recent flu-like symptoms and pregnancy