Representations and Acceptability of HIV Therapeutic Vaccine in a Cohort of HIV-1 Infected Outpatients Followed at Hospital
Condition: HIV
Study type: Interventional

Summary: 
      The main objective of the study is to assess the acceptability of a future therapeutic
      vaccine against HIV in patients living with HIV-1.

      Secondary objectives concern the validation of a specific questionnaire for self-perception
      and acceptability of therapeutic vaccination against HIV-1 (RAVVIH), the development of a
      composite score for acceptability based on this questionnaire, and the analysis of critical
      factors related to: representations of vaccination in general, representations of therapeutic
      vaccination specific to HIV, perception of disease severity, health-related quality of life,
      doctor-patient relationship.
    

Detailed description: 
      Since 2000, the study of the acceptability of HIV vaccine candidates is one of four major
      areas recommended by the WHO. Presently, there are several studies in HIV field on the theme
      " Cure ". However, no study has yet addressed the question of the acceptability of
      therapeutic vaccine candidates against HIV who are currently already in clinical trials phase
      2 and 3 In addition, many aspects of the disease, its treatment and living conditions of
      PLWHA could affect the acceptability of such a vaccine

      Description of the study population :

      The study population has the characteristics of the HIV population living in France [ 26, 27
      ] .The French population reported by the database of the French Hospital in 2011 FHDH
      comparable to the population of their study ( three centers combined ) :- 36% of MSM- 9.1% of
      injection drug users (IDUs) 45% of heterosexuals : Europe including France 23.7% of
      immigrants from sub-Saharan Africa. 88 % were receiving antiretroviral therapy and 95% are
      undetectable .- 40 % are between 40-49 years

      Description of the research methodology

      Quantitative study : Patients complete questionnaires validated and published in the
      literature: Brief IPQ R and HIV PROQOL[ 28, 29 ] .The questionnaire RAVVIH therapeutic
      vaccine has been designed from the literature review , and the opinions ofScientific Council
      in particular Dr. Pierre Verger social scientist vaccination and experts on the perception of
      patients. It was tested on a sample of 15 PHAs.The questionnaire takes into account several
      important dimensions that could affect therapeutic vaccine acceptability :

        1. the individual history , ARV treatment (tolerance ) and the perception of related
           adverse symptoms treatment

        2. compliance with respect to ARV treatment

        3. the quality of the relationship of the person with his or her physician ( referent ,
           general ) and the level ofit gives them confidence ; 4 ) the level of social support
           person (unlike its isolation ) that may explain the desire to participate in a trial
           (more attention in the context of a trial , for example ... ) 5 ) managing the secret of
           his illness ( to avoid taking daily treatment with a vaccine therapy, can be a way to
           reduce the opportunities to reveal his illness ... )6) the perception of the seriousness
           of his illness.T

      Qualitative study : A group of 20 patients will be offered a qualitative interview with a
      psychologist. The interview guide was developed from the literature and expert community.
      Volunteers will be recruited according to the different categories of people representative
      of the HIV population in France.

      Study participation is approximately 30 minutes, including the presentation of protocol and
      the charging time of the questionnaire.

      After giving consent in the study, the patient may at any time withdraw it and end its
      participation.

      Paper questionnaires completed by the patients will be considered as source documents for
      this study and the patient's medical record where the following data will be collected (date
      of birth, viral load , therapy; vaccination status , mode of infection , nadir CD4 ,CD4 count
      , year of diagnosis , year of start of HAART, HBV and HCV co-infection status).

      Quality assurance plan / Study Monitoring and Auditing :

      This study will follow the monitoring and auditing guidelines designed by the sponsor in
      order to ensure agreement with good clinical practices recommendations.

      Study monitoring and source data verification :

      Monitoring will be achieved by a representative from the sponsor (Clinical Research Delegate)
      who will perform on-site visits during which s/he will compare data from the observation
      booklet with source data in order to assess its completeness. The clinical research delegate
      will ensure that, via frequent communication (either by mail, phone, fax, and email), the
      research is in agreement with the protocol and complies with regulation.

      The site closing visit will be performed by the Clinical Research Delegate.

      Site Monitoring : The national regulatory board and/or the representatives of the sponsor's
      Clinical Quality Board will be able to request access to source data, observation booklets,
      and all study documentation during site auditing or inspection. The investigator has to
      guarantee unhindered direct access to all the above-mentioned documentation and collaborate
      fully to site auditing and inspections. Medical files and all study documentation will be
      available for photocopy during site auditing and inspections, as long as subjects' names are
      hidden on the copy in order to maintain confidentiality.

      Statistical Analysis

      Analysis of Main Variable :

      Acceptability Score will be summarized using a mean and a median as well as the usual
      indicators of variability (standard deviation, inter-quartile range, and range). The
      investigators will pay particular attention to the symmetry of the distribution: a strong
      asymmetry will suggest that the scale is not an optimal tool to measure acceptability in this
      sample. The analysis will be stratified in the following sub-groups: investigation site, sex,
      age, and duration of the disease.

      Validation of the RAVIVIH Acceptability Questionnaire : Distribution of the answers, on a
      Likert scale, to each of the questionnaire items will be assessed through a relative
      frequency table in order to determine if a ceiling/flooring effect is present (i.e. more than
      80% of the respondents into either extremes of the Likert scale).

      Since the questionnaire is built into blocks (knowledge, perceptions, acceptability), a
      principal component analysis (PCA) will be performed to verify that the correlation structure
      of the questionnaire items' answers can allow the identification of specific dimensions. In
      case of strong asymmetry on the questionnaire, the analysis could be completed by a
      non-linear PCA. This analysis will also allow to assess the relation of questionnaire's items
      to acceptability and thus to justify the use of a composite score based on the answers to
      acceptability items. To make the interpretation of such an acceptability score easier, each
      score will be linearly translated to a 100-point scale.

      In addition to this assessment of the RAVIVIH questionnaire's construction validity, a
      multitrait scaling will be performed. It will aim to verify that the correlation between
      items from the same dimension are appropriate (> 0.5) and that correlation between items
      belonging to unrelated dimensions remains low (<0.2). The statistical significance of the
      linear correlations will be tested with a Pearson correlation test, and correlation for
      multiple tests with the Bonferroni method.

      Acceptability Score Validation The investigators will validate the RAVIVIH composite score
      (in its 100-point scale form) by comparing it with the EVA questionnaire using linear
      correlation coefficient (Pearson) and Spearman's rank correlation coefficient. The latter can
      assess the degree to which a relationship between two variables can be described by a
      monotonic function.

      Influence of knowledge and perception of therapeutic vaccine and biomedical data on
      Acceptability To determine if variations in the degree of acceptability can be explained by
      differences in knowledge or perceptions, a canonical multivariate analysis will be performed
      in order to identify which items share the greatest contribution in explaining variations in
      the acceptability score.

      Multiple correlation analyses will be performed in order to verify the association between
      the acceptability score and biomedical characteristics as well as quality of life as measured
      by the PROQOL-HIV questionnaire. Scores translating into "social relationships", "sexual
      relationships", "stigma", and "impact of treatment" dimensions will be of part interest. This
      analysis will provide, indirectly, an indication of the RAVIVIH questionnaire's convergent
      validity. The RAVIVIH acceptability score will also be correlated with the IPQ-R score.

      Sample size assessment (total and by site) Since this study is essentially a prospective one
      and since it is based on a representative sample of French HIV-positive patients, the number
      of participants necessary was determined based on the required precision for the main
      indicator of therapeutic vaccine acceptability.

      A sample size of 200 (N=200) allows to estimate an average acceptability score on the EVA
      questionnaire with a margin of error inferior to 0.5 (95% confidence interval), assuming a
      theoretical 1-point standard deviation. Regarding the composite acceptability score,
      referring to the scoring system used by Newman (2011) and assuming a standard deviation of 20
      points, this translates into an average on a 100-point scale with 3-point accuracy.
      Furthermore, such a sample size would allow the calculation of the PCA and the extraction of
      3 or 4 components.

      Expected statistical significance : For all calculations and statistical tests, a 95%
      confidence interval will be applied.

      Plan for missing data :

      Missing data include variables that are reported as missing, unavailable, "non-reported",
      uninterpretable, or considered missing because of data inconsistency or out-of-range results.
      The Clinical Trial Technician or the physician will inspect the questionnaire during the
      consult to ensure that no items are left unanswered. If, despite this procedure, items are
      left unanswered, a system will be implanted so as to be able to retrieve the data necessary
      for statistical analysis.

      Management of Modifications brought to the Initial Statistical Analysis Plan :

      Modifications brought to the initial statistical analysis plan will be reported in a written
      document that will be attached to the initial plan. If additional statistical analysis became
      necessary, it would be detailed in the analysis report.
    

Intervention name(s): Questionnaire; Interview
Intervention type(s): Other; Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: HIV; Therapeutic vaccine; acceptability; representations