Inducing Immune Quiescence the Genital Tract With ASA (IIQ-2)

Preventing HIV Infection by Targeting the Immune System Instead of the Virus

There are 33.4 million individuals living with HIV/AIDS worldwide. Despite successful HIV prevention strategies such as condom use and reduction of sexual partners, HIV continues to spread at an alarming rate. In 2010, 2.6 millions of new infections were detected. In Sub-Saharan Africa, women represent the two-third of all new infections1. Despite the efforts of the scientific community, there is still no commercial vaccine or microbicide available.

To explain this natural protection against HIV, different mechanisms have been identified. These women have a unique immune phenotype that we called Immune Quiescence. 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 This project aims to induce an Immune Quiescence phenotype (decreasing immune activation) to prevent HIV infection

Study Overview

• Status: Recruiting
• Conditions: HIV
• Intervention / Treatment: Drug: ASA 325mg; Other: Control Group; Drug: ASA 81mg

Detailed Description

HIV is an important global health issue. Globally, HIV is mostly transmitted through heterosexual sexual activity, and women bear the brunt of the pandemic as two-third are in women. New preventive strategies need to be developed to empower women to protect themselves. In Nairobi, Kenya, there are around 27 000 sex workers and despite prevention efforts, HIV incidence is very high in this vulnerable group which serves as catalyzers for HIV transmission to the community. Among those sex workers, despite being at higher risk of infection, some rare individuals remain HIV exposed seronegative (HESN). Over the years, our group has tried to understand this natural protection to HIV infection. The investigators discovered that in HESN individuals, the basal level of activation of the immune system is lower than in other people. This includes having few HIV target cells, mainly CD4+ CCR5+ T cells, in their genital tract. The investigators called this special phenotype Immune Quiescence (IQ). In a recent pilot study (Limiting HIV target cells by Inducing Immune Quiescence in the female genital tract ) the investigators showed that in non-sex worker women it is possible to decrease the proportion of HIV target cells and/or HIV co-receptor at the female genital tract by using anti-inflammatory drugs.

Herein, the investigators are proposing to conduct a follow-up study in female sex workers to determine the best drug formulation and drug size effect on reducing HIV target cell number at the female genital tract (FGT). Participants will receive acetylsalicylic acid (ASA) (81mg/day), ASA (325mg/day), or nothing for five months. At visit 1, the baseline immune activation level of the participants will be determined. In this way, every woman will serve as her own control thereby reducing the variation between tested and control groups. Participants will be randomized and ask to take the drug daily. Participants will be followed on a monthly basis. At each study visit, blood, cervico-vaginal lavage and cervical cells will be taken to determine the level of immune activation. This study is a critical "second step" in the rational development of HIV preventive biomedical method.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Keith R Fowke, PhD; Phone Number: 204-789-3296; Email: keith.fowke@umanitoba.ca
• Study Contact Backup: Name: Julie Lajoie, PhD; Phone Number: 204-789-3296; Email: julie.lajoie@umanitoba.ca

Study Locations

• Kenya
  • Nairobi,, Kenya
    • Recruiting
    • Kenyan Aids Control Project/University of Nairobi
    • Contact: Joshua Kimani, Dr.; Email: jkimani@csrtkenya.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age greater of 18 years and less than 45
• Be active in sex work for five years or less
• Uterus and cervix present
• Willing to take daily the study drug (acetylsalicylic acid)
• 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

Exclusion Criteria:

• Age less than 18 or more than 45
• Breastfeeding
• Pregnant in the last 12 months
• Presence of sexual transmissible disease or bacterial vaginosis at enrollment
• Menopausal
• Pregnancy (if a women becomes pregnant during the study she will be excluded)
• Not being involve in sex work or being involved in sex work for more than 6 years
• Having a chronic disease
• Consumption of the medication listed in appendix entitled: list of other medication for health conditions
• Being allergic to acetylsalicylic acid, other medication for pain or fever, tartrazine 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ASA 325mg; Daily uptake of 325mg ASA	Drug: ASA 325mg; Participants will be randomized to take 325mg orally on a daily basis for a duration of 6 months; Other Names: Acetylsalicylic acid 325mg
Active Comparator: No drug; no drug	Other: Control Group; Participants will be randomized to take nothing on a daily basis for a duration of 6 months; Other Names: no drug
Active Comparator: ASA 81mg; daily uptake of 81mg ASA	Drug: ASA 81mg; Participants will be randomized to take 81mg orally on a daily basis for a duration of 6 months; Other Names: Acetylsalicylic acid 81mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the proportion of HIV Target cells (CD4+CCR5+)	Fresh cervical mononuclear cell populations from the cytobrush/scraper will be stained with monoclonal antibodies, and analyzed by flow cytometry. Proportion of CD4+CCR5+ T cells will be assessed at baseline and over the course of the study.	Baseline and at each month; For six months following enrolment

Collaborators and Investigators

• Sponsor: University of Manitoba

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: HS19749(B2016:042); B2016:042 (Other Identifier: University of Manitoba)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: we are not planing to share individuals data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No