Inducing Immune Quiescence to Prevent HIV Infection in Women (IIQ)

University of Manitoba

Status

Completed

Conditions

HIV

Treatments

Drug: Hydroxychloroquine (HCQ)

Drug: Acetylsalicylic Acid (ASA)

Study type

Interventional

Funder types

Other

Identifiers

NCT02079077

B2013:042

MOP#86721 (Other Grant/Funding Number)

S5-0386-01 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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:

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.)

.

Enrollment

91 patients

Sex

Female

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Age greater than 18 years old and less than 50 years old
Uterus and cervix present
Willing to take daily acetylsalicylic acid or HCQ
Willing to undergo pelvic exams
In general good health, no chronic infection and not taking any anti-inflammatory or immunosuppressors
Being HIV negative
Without any cardiovascular disease
Being active in sex work (for the Female commercial sex worker group)

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