Inducing Immune Quiescence to Prevent HIV Infection in Women
Condition: HIV
Study type: Interventional

Summary: 
      In this project, the investigators want to analyse the capacity of Acetylsalicylic acid and
      hydoxychlroquin (HCQ) to induce an Immune Quiescence (IQ) phenotype, which has been
      previously associated with natural protection to HIV infection. This phenotype is
      characterized by lower expression of genes involved in cellular activation, lower resting
      levels of inflammatory cytokine production, lower level of systemic activated T cells,
      increased levels of systemic T regulatory, increased production of anti-viral anti-protease
      serpins at the female genital tract and reduced numbers of HIV target cells (mainly CD4+
      CCR5+ T cells) in the FGT ( female genital tract).

      The objective of this study is to determine if daily oral administration of Acetylsalicylic
      acid or hydroxychlroroquin can reduce systemic and mucosal immune activation in HIV negative
      women.
    

Detailed description: 
      The investigators will enrol 80 non female sex work low-risk HIV negative women and 80 HIV
      negative female sex worker HIV negative form Nairobi, Kenya and followed for a 3 months
      period.

      During the first month, samples will be taken on a monthly basis

        -  blood,

        -  vaginal samples: cytobrush/scarper and cervico vaginal lavage (CVL). This is done to
           determine the baseline levels of systemic and mucosal immune activation of each woman.
           In this way, every women is acting as her own control thereby reducing variation between
           control and participant.

      Chemokine/cytokine level, as well as cellular immune activation and T regulatory cells will
      be assessed.

      At month two: the women will be divided in two different arms (oral administration of
      hydroxychloroquine: 200mg/day or Acetylsalicylic acid 81mg/day) and followed, on a monthly
      basis, for an 8 additional weeks.

      During this time, monthly blood and vaginal samples (cytobrush/scraper and CVL) the
      investigators will be taken. They will measure change in the systemic and mucosal immune
      activation.

      Immune Quiescence phenotype (decrease of T cells immune activation, lower immune genes
      activation expression and pro-inflammatory cytokine/chemokine expression) will be evaluated
      by flow cytometry, microarray, and multiplex bead array technology.

      Here is how samples will be taken:

        1. A sample of cervical mucus will be collected by using a cotton swab rotated 360º in the
           cervical os, and a second swab used to collect secretions from the posterior vaginal
           fornix. Both swabs will be transferred into a single vial containing 5 mL of
           phosphate-buffered saline (PBS) which will be transported to the laboratory to be tested
           and cultured for sexually transmitted infections such as gonorrhea, chlamydia etc.

        2. Cervical cells will be collected by using a small brush and a wooden spatula. Both
           specimen will be transferred into a 15ml conical tube containing 5 ml of PBS. This
           specimen will be used to characterize the cellular populations in the specimen.

        3. Cervico vaginal lavage will be performed by washing the endocervix with 2 ml of sterile
           1x PBS. The liquid will be collected form the posterior fornix. Samples will be placed
           into a conical tube, centrifuged to remove cellular debris and the supernatant will be
           stored at -70°C and will be shipped in liquid nitrogen dry shipper to Winnipeg,
           Manitoba. Those specimens will be used for innate soluble factor detection (chemokines,
           cytokines, antibodies, innate protein, etc

        4. 30ml of venous blood will be taken. (Peripheral Blood Mononuclear Cells will be
           extracted for immune activation analysis, DNA will be used for immune genes expression,
           plasma will be used for protein and innate soluble factor detection.)

           .
    

Intervention name(s): Acetylsalicylic Acid (ASA); Hydroxychloroquine (HCQ)
Intervention type(s): Drug; Drug
Intervention description(s): Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months; Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months.
Intervention MeSH terms: Aspirin; Hydroxychloroquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: HIV, Immune quiescence, ASA, Hydroxychloroquin