Understanding HIV Susceptibility in the Female Genital Tract

There is great variability in susceptibility from one person to another, and less than one in a hundred sexual exposures to HIV results in infection. In addition, some recent trial of methods to prevent HIV - including vaccines and microbicides - have actually increased HIV acquisition among trial participants for reasons that we do not fully understand. While we know that immune differences in the genital lining are an important determinant of whether a person is infected after a sexual HIV exposure, we don't know enough about these differences to be able to accurately assess a person's individual HIV risk. Therefore, the development of safe and non-invasive laboratory tests to estimate a person's susceptibility in the genital tract would be useful in clinical studies of new HIV prevention tools.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: Vaginal and blood sample collection

Detailed Description

Heterosexual intercourse is the most common mode of transmission of HIV, but the risk of HIV acquisition after exposure is so low that studies to assess HIV risk must have a huge sample size. The goal of this study is to assess the suitability of a prototype pseudovirus assay to identify early HIV target cells in the female genital tract, using cervical cytobrush samples collected from healthy women, and to optimize assay sensitivity.

This novel HIV entry assay may overcome the need for a large sample size by directly measuring how susceptible a person is by using a sample similar to a PAP test. The assay is performed on immune cells obtained from a cervical cytobrush and enables assessment of HIV cell entry within 24 hours. If the assay works, this technique may have the potential to assess the impact of clinical parameters such as stage of menstrual cycle, or sexually transmitted infections and their treatment on HIV susceptibility in the female genital tract. Therefore, the assay may serve as an important monitoring tool in clinical trials of HIV prevention, serving as an invaluable intermediate endpoint to assess HIV acquisition risk, rather than relying on actual participant HIV seroconversion/infection.

• Study Type: Observational
• Enrollment (Actual): 98

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

This study is recruiting healthy non-pregnant women from the St. Michael's Gynecology clinic.

Description

Inclusion Criteria:

• women over the age of 18 years

Exclusion Criteria:

1. pregnant
2. actively menstruating
3. known HIV infection
4. genital ulceration or discharge on history or physical examination

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD4 cell infection	The absolute number of CD4+ cells per cytobrush that are infected by HIV	Assay to be conducted within 24 hours of sample collection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of infected CD4 cells	Nature of the CD4+ cells that are infected, ie: identification of immune characteristics that are associated with preferential HIV cell entry. Parameters to be assessed include immune activation markers and the expression of HIV coreceptors and integrins.	Assay to be conducted within 24 hours of sample collection

Collaborators and Investigators

• Sponsor: Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: February 22, 2017
• First Submitted That Met QC Criteria: February 22, 2017
• First Posted (Actual): February 27, 2017

Study Record Updates

• Last Update Posted (Actual): February 22, 2019
• Last Update Submitted That Met QC Criteria: February 20, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; HIV Infections; Disease Susceptibility
• Other Study ID Numbers: 14-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No