Contraceptive/HIV Affecting Risk in Adolescents (CHARA)

This study will evaluate the impact of hormonal contraceptives on HIV risk associated with changes to the innate immunity in the female genital tract in a cross-sectional study. HIV risk will be evaluated by the capacity of cervical tissue to replicate HIV when challenged ex vivo and correlated to the number of CD4 T cells, DCs, and macrophages; the capacity of cervicovaginal fluid to inhibit HIV will be correlated to soluble mucosal mediators, and the vaginal microbiota. The lower genital tract samples will be collected from 120 adolescents aged 18-19 (40 using no hormonal contraception, 40 using ENG-I, 40 using LNG-IUS). For comparison, 90 adult women aged 25-45 will be equally distributed between the same groupings.

Study Overview

• Status: Terminated
• Conditions: Hiv; Contraception

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital of UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

non-pregnant, HIV negative, healthy 18-19 year old women and 25-45 year old women

Description

Inclusion Criteria:

1. Meets one of the following age groups (at the time of sample collection):

   1. Adolescent aged 18-19
   2. Adult aged 25-45

2. Meets one of the following contraception groups:

   1. Regular menstrual cycles by participant history (if not using hormonal contraception)
   2. Use of ENG-I (i.e. Implanon/Nexplanon) for at least 30 days by participant history
   3. Use of LNG-IUS (Mirena or Skyla) for at least 30 days by participant history
3. HIV uninfected Note: HIV testing will be done as part of screening. However, if a woman participated in a recent research study and has an HIV test result available from that study, this will suffice provided the date of the test is within 6 months of the study visit.
4. Willing to undergo pelvic exam and collection of cervical biopsies
5. Willing to provided written informed consent
6. Agree to be sexually abstinent for 48 hours prior to the cervical biopsies and for one week after the biopsies.

Exclusion Criteria:

1. Use of any other hormonal contraception other than ENG-I or LNG-IUS
2. Use of a diaphragm or spermicide for contraception
3. Pregnant or pregnancy within 90 days
4. Currently breastfeeding
5. Currently menstruating/bleeding (at time of specimen collection) Note: participant can return after cessation of bleeding for specimen collection
6. Past participation in more than one study involving cervical biopsies per participant report
7. Cervical biopsies within one month of specimen collection visit
8. Abnormal vaginal discharge or other genital tract symptoms at the time of specimen collection
9. Pelvic findings on the day of specimen collection consistent with cervicitis (i.e. MPC, erythema, edema) or anatomy making cervical biopsies difficult
10. Menopausal
11. Hysterectomy
12. History of malignancy of the genital tract (including cervix, uterus, vagina, and vulva)
13. History of immunosuppression (including HIV infection, diabetes, and chronic steroid use)
14. Known history of a platelet/bleeding/clotting disorder
15. Use of a systemic or vaginal antimicrobial agent within 7 days of specimen collection
16. Use of any vaginal product (i.e. douching, spermicide, lubricant) or device within 7 days of specimen collection Note: tampon use is acceptable
17. Any other condition that in the opinion of the Study Investigator would preclude provision of informed consent or make study participation unsafe, complicate the interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort
No contraception/18-19 years old
Use of ENG-I/18 - 19 years old
LNG-IUS/18-19 years old
No Contraception/ 25 - 45 years old
Use of ENG-I/25 - 45 years old
LNG-IUS/25-45 years old

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV replication in cervical tissue as measured by levels of HIV p24/viral transcripts	cervical tissue testing	baseline
number of immune cells in cervical tissue, including CD45, CD3, CD4, and CD8 and their expression of CCR5, CCR6 and CD69, and CD11c+ DCs and CD14+ macrophages	cervical tissue testing	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of bacterial vaginosis defined as a Nugent score ≥7 on a vaginal smear	vaginal specimen	baseline
prevalence and quantity of lactobacillus species and bacterial vaginosis associated bacteria as measured by traditional culture methods and quantitative PCR	vaginal specimen	baseline
HIV inhibitory activity in mucosal fluid; and soluble mucosal factors identified through pathway analyses and confirmed by targeted ELISA/multiplexing technology (proteases/ anti-proteases, keratin, IFNε, and other molecules)	mucosal fluid	baseline

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 31, 2017
• Primary Completion (ACTUAL): September 17, 2018
• Study Completion (ACTUAL): September 17, 2018

Study Registration Dates

• First Submitted: August 8, 2017
• First Submitted That Met QC Criteria: September 28, 2017
• First Posted (ACTUAL): October 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 7, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: PRO17050002

Drug and device information, study documents

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