Inducing Immune Quiescence to Prevent HIV Infection in Women

NCT02079077 | Completed Results DMC

• 3 other identifiers: B2013:042MOP#86721S5-0386-01
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV

Keywords

HIV, Immune quiescence, ASA, Hydroxychloroquin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Change in Number of CCR5+CD4+ T Cell Population at the Female Genital Tract.

  baseline and 8 weeks

Study Arms (2)

Acetylsalicylic Acid (ASA)

OTHER

ASA 81 mg. p.o. daily for two months

Drug: Acetylsalicylic Acid (ASA)

Hydroxychloroquine (HCQ)

OTHER

Hydroxychloroquine (HCQ) 200 mg. o.d. p.o. for two months.

Drug: Hydroxychloroquine (HCQ)

Interventions

Acetylsalicylic Acid (ASA) DRUG

Acetylsalicylic Acid (ASA) 81 mg. oral daily for two months

Acetylsalicylic Acid (ASA)

Hydroxychloroquine (HCQ) DRUG

Hydroxychloroquine (HCQ) 200 mg. oral, daily for two months.

Hydroxychloroquine (HCQ)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Manitoba: lead
• University of Nairobi: collaborator

Study Sites (1)

Kenyan Aids Control Project/University of Nairobi

Nairobi, Kenya

Location

Related Publications (2)

• 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.

  PMID: 34868050 DERIVED

• 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.

  PMID: 28893304 DERIVED

MeSH Terms

Interventions

Aspirin; Hydroxychloroquine

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Keith Fowke
• Organization: University of Manitoba

keith.fowke@umanitoba.ca

204-789-3296

Study Officials

• Keith R. Fowke, PhD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Department of Medical Microbiology

Study Record Dates

• First Submitted: March 3, 2014
• First Posted: March 5, 2014
• Study Start: April 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2018
• Last Updated: October 10, 2019
• Results First Posted: October 10, 2019

Record last verified: 2019-09

Locations

KE (1)