Vaginal Innate Immunity in Normal and HIV-Infected Women

The innate immunity of the vaginal tract provides first-line defense from abnormal microorganisms or overgrowth of common organisms, such as Candida species or Gardnerella vaginalis. It is unclear from the current available literature whether the rate of vaginal infection increases or decreases in frequency during pregnancy when compared to the non-pregnant state, but this may be predicted by shifts in vaginal innate immunity. Vaginal infections are important players in HIV disease, potentially increasing the risk of viral transmission. In addition, these infections may activate inflammatory markers in the reproductive tract and increase the risk of premature delivery or other negative pregnancy outcomes. The vaginal innate immune system has not been well characterized in pregnant women, or in women with HIV infection. The study of how this system changes in pregnancy and HIV infection will provide essential knowledge for further study of vaginal mucosal protection.

The investigators study is an observational study designed to compare levels of vaginal innate immunity markers in women based on a) pregnancy status and b) HIV infection status. Comparisons will be made between pregnant and non- pregnant women and between HIV positive and HIV negative women. The investigators hypothesize that there will be significant differences in levels of innate immunity between the groups.

Study Overview

• Status: Completed
• Conditions: Pregnancy; HIV
• Intervention / Treatment: Other: Vaginal lavage specimen

• Study Type: Observational
• Enrollment (Actual): 83

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Healthy women, 18 to 40 years old, with spontaneous menstrual cycles or with normal ongoing pregnancy with gestational age between weeks 13 - 30 and able to provide informed consent

Description

Inclusion Criteria:

• Female
• Age 18 - 40 years
• Able to provide informed consent

Exclusion Criteria:

• Women with the following conditions will be excluded:
• Currently active Syphilis or Herpes simplex infection
• Other (non-HIV) comorbid conditions causing acute or chronic inflammatory states or immunosuppression (i.e., transplant recipients, active systemic lupus)
• Current use of hormonal birth control or with IUD in place
• History of Hysterectomy or bilateral oophorectomy

Women with the following conditions will require rescheduling of the study visit:

• Use of hot tub or pool, vaginal creams, douches, vaginal medications, or vaginal intercourse within 48 hours
• Current vaginal bleeding
• Recent treatment for vaginal infection will require 4 - 6 week delay in enrollment

Pregnant women with the following conditions at the time of examination will be excluded:

• Active labor or other conditions of duress
• Signs or symptoms of preterm labor
• Vaginal bleeding
• Placenta previa
• History of prior preterm birth
• Ruptured amniotic membranes
• Multifetal gestation
• Stillbirth or intrauterine fetal demise (IUFD)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant, HIV- negative; This cohort has completed accrual as of 12/28/11.	Other: Vaginal lavage specimen; Collection of 3cc of saline used in the vagina to collect innate immunity markers
Pregnant, HIV-positive	Other: Vaginal lavage specimen; Collection of 3cc of saline used in the vagina to collect innate immunity markers
Non-pregnant, HIV-negative; This cohort has completed accrual as of 12/28/11.	Other: Vaginal lavage specimen; Collection of 3cc of saline used in the vagina to collect innate immunity markers
Non-pregnant, HIV-positive; This cohort has completed accrual as of 12/28/11.	Other: Vaginal lavage specimen; Collection of 3cc of saline used in the vagina to collect innate immunity markers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the vaginal concentrations innate immunity markers (alpha / beta interferons, defensin, cathelicidin, lysozyme, lactoferrin, and SLPI) in pregnant and non-pregnant women who are HIV-negative.	Investigators will quantify the major vaginal innate immunity markers, including type 1 (alpha and beta) interferons, defensins, cathelicidins, lysozyme and lactoferrin, and secretory leukocyte protease inhibitor (SLPI). These antimicrobial host defense peptides are produced by genital tract mucosal epithelial cells and associated immune cells, and have a wide range of antiviral, antibacterial, antifungal and antiparasitic activities and modes of action. We hypothesize that changes in innate immunity markers take place during pregnancy, thereby changing native vaginal immunity.	up to 2 clinic visits in 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the vaginal concentrations of innate immunity markers (alpha and beta) interferon, defensin, cathelicidin, lysozyme, lactoferrin, and SLPI)) in HIV-positive pregnant and non-pregnant women	Investigators will quantify the major vaginal innate immunity markers, including type 1 (alpha and beta) interferons, defensins, cathelicidins, lysozyme and lactoferrin, and secretory leukocyte protease inhibitor (SLPI). Women who have HIV may express different innate immunity marker profiles in vaginal secretions when pregnant as compared to non-pregnant HIV positive women. Timing of specimen collection: In pregnancy: Weeks 13 - 30. Non-pregnant: 3 weeks between menstrual bleeding cycles	up to 2 clinic visits in 10 weeks
To compare the vaginal concentrations innate immunity markers (alpha / beta interferons, defensin, cathelicidin, lysozyme, lactoferrin, and SLPI) in pregnant women who are HIV-negative to pregnant women who are HIV-positive.	Investigators will quantify the major vaginal innate immunity markers, including type 1 (alpha and beta) interferons, defensins, cathelicidins, lysozyme and lactoferrin, and secretory leukocyte protease inhibitor (SLPI). Women with HIV may express different innate immunity marker profiles in vaginal secretions when pregnant as compared to pregnant, HIV-negative women. This may provide some explanation for differences in vaginal infection rates between the groups. Timing of specimen collection: In pregnancy: Weeks 13 - 30.	up to 2 clinic visits in 10 weeks

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Investigators: Principal Investigator: Jennifer Ballard Dwan, M.D., Boston University; Principal Investigator: Deborah Anderson, Ph.D., Boston University

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: October 29, 2010
• First Submitted That Met QC Criteria: March 16, 2011
• First Posted (Estimate): March 18, 2011

Study Record Updates

• Last Update Posted (Estimate): May 9, 2016
• Last Update Submitted That Met QC Criteria: May 5, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: HIV; pregnancy; innate immunity; vaginal immunity
• Other Study ID Numbers: H-29331