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| ID | Type | Description | Link |
|---|---|---|---|
| MOP#86721 | Other Grant/Funding Number | Canadian Institue of Health Research | |
| S5-0386-01 | Other Grant/Funding Number | Grand Challenge Canada |
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| Name | Class |
|---|---|
| University of Nairobi | OTHER |
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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.
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
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.)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acetylsalicylic Acid (ASA) | Other | ASA 81 mg. p.o. daily for two months |
|
| Hydroxychloroquine (HCQ) | Other | Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acetylsalicylic Acid (ASA) | Drug | Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Systemic Immune Activation From Baseline Observed by the CD69 Expression on CD4 T Cells | We will analyse reduce of immune activation by measuring change in T cell activation (CD69) between baseline and every month during drug administration phase (8 weeks). | Baseline and 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Number of CCR5+CD4+ T Cell Population at the Female Genital Tract. | We will measure changes in the number of CD4+T cells expressing CCR5 at the female genital tract before and at the end of the study. | baseline and 8 weeks |
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Inclusion criteria:
Exclusion criteria:
Age less than 18 years or more than 50 years old
Pregnancy (if a women becomes pregnant during the 10 weeks of the project she will be excluded)
Breast feeding
Pregnant in the last 12 months
Being positive for Sexual transmissible disease or bacterial vaginosis at week 0
Menopausal
No longer involve in sex work (for the female sex worker group)
Having a chronic disease
Taking any of the medication listed in annex 1 for health conditions
Being allergic to acetylsalicylic acid, other medication for pain or fever, tartrazine dye or chloroquine, hydroxuchloroquine, primaquine or any other medication
Having heartburn, stomach pain, stomach ulcer, anemia, hemophilia, kidney or liver disease, psoriasis, porphyria or other blood disease, G-6-PD deficiency, dermatitis (skin inflammation), alcoholism
Having experienced previous vision changes while taking chloroquine, hydroxychloroquine (Aralen) or primaquine.
Having a history of a diagnosed cardiovascular event, heart failure, peripheral arterial disease, angina, stoke, transient ischemic attack
Having a current or recurrent condition with a high risk of major bleeding
Having anemia
Current participation in a clinical trial
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| Name | Affiliation | Role |
|---|---|---|
| Keith R. Fowke, PhD | University of Manitoba | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kenyan Aids Control Project/University of Nairobi | Nairobi | Kenya |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34868050 | Derived | Lajoie J, Kowatsch MM, Mwangi LW, Boily-Larouche G, Oyugi J, Chen Y, Kimani M, Ho EA, Kimani J, Fowke KR. Low-Dose Acetylsalicylic Acid Reduces T Cell Immune Activation: Potential Implications for HIV Prevention. Front Immunol. 2021 Nov 18;12:778455. doi: 10.3389/fimmu.2021.778455. eCollection 2021. | |
| 28893304 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | Acetylsalicylic Acid (ASA) | ASA 81 mg. p.o. daily for two months Acetylsalicylic Acid (ASA): Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months |
| FG001 | Hydroxychloroquine (HCQ) | Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months. Hydroxychloroquine (HCQ): Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
study population was women from the general population in general good health and HIV negative
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| ID | Title | Description |
|---|---|---|
| BG000 | Acetylsalicylic Acid (ASA) | ASA 81 mg. p.o. daily for two months Acetylsalicylic Acid (ASA): Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months |
| BG001 | Hydroxychloroquine (HCQ) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Changes in Systemic Immune Activation From Baseline Observed by the CD69 Expression on CD4 T Cells | We will analyse reduce of immune activation by measuring change in T cell activation (CD69) between baseline and every month during drug administration phase (8 weeks). | general population | Posted | Mean | Standard Deviation | percentage of cells | Baseline and 8 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Acetylsalicylic Acid (ASA) | ASA 81 mg. p.o. daily for two months Acetylsalicylic Acid (ASA): Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Keith Fowke | University of Manitoba | 204-789-3296 | keith.fowke@umanitoba.ca |
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| ID | Term |
|---|---|
| D001241 | Aspirin |
| D006886 | Hydroxychloroquine |
| ID | Term |
|---|---|
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
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| Hydroxychloroquine (HCQ) | Drug | Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months. |
|
| Lajoie J, Mwangi L, Fowke KR. Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention. AIDS Res Ther. 2017 Sep 12;14(1):46. doi: 10.1186/s12981-017-0166-7. |
Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months.
Hydroxychloroquine (HCQ): Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| T cell immune activation | Mean | Standard Deviation | percentage of cells |
|
|
|
| Secondary | Change in Number of CCR5+CD4+ T Cell Population at the Female Genital Tract. | We will measure changes in the number of CD4+T cells expressing CCR5 at the female genital tract before and at the end of the study. | Posted | Median | Standard Deviation | percentage of cells | baseline and 8 weeks |
|
|
|
| 0 |
| 43 |
| 0 |
| 43 |
| EG001 | Hydroxychloroquine (HCQ) | Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months. Hydroxychloroquine (HCQ): Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months. | 0 | 48 | 0 | 48 |
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| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |