Inducing Immune Quiescence to Prevent HIV Infection in Women (IIQ)
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|ClinicalTrials.gov Identifier: NCT02079077|
Recruitment Status : Active, not recruiting
First Posted : March 5, 2014
Last Update Posted : June 23, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|HIV||Drug: Acetylsalicylic Acid (ASA) Drug: Hydroxychloroquine (HCQ)||Not Applicable|
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
- 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:
- 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.
- 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.
- 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
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.)
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||77 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Limiting HIV Target Cells by Inducing Immune Quiescence in the Female Genital Tract|
|Study Start Date :||April 2014|
|Actual Primary Completion Date :||December 2015|
|Estimated Study Completion Date :||December 2018|
Acetylsalicylic Acid (ASA)
ASA 81 mg. p.o. daily for two months
Drug: Acetylsalicylic Acid (ASA)
Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months
Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months.
Drug: Hydroxychloroquine (HCQ)
Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months.
- Change in systemic immune activation from baseline observed by a decrease of HLA-DR and CD69 expression on CD4 T cells [ Time Frame: Baseline and 8 weeks ]We will analyse reduce of immune activation by measuring change in T cell activation (HLA-DR and CD69) and the systemic pro-inflammatory immune environment (cytokine and chemokine) between baseline and every month during drug administration phase (8 weeks).
- Change in number of HIV target cells from baseline by reduction of CCR5+CD4+ T cell population at the female genital tract. [ Time Frame: baseline and 8 weeks ]We will measure CCR5 expression on CD4+T cells the female genital tract before and at the end of the study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02079077
|Kenyan Aids Control Project/University of Nairobi|
|Principal Investigator:||Keith R. Fowke, PhD||University of Manitoba|